bluuebunny/crossref_metadata_2025 huggingface dataset:
Two‐Year Remission and Subsequent Relapse in Children with Newly Diagnosed Epilepsy
Authors: Berg Anne T. , Shinnar Shlomo , Levy Susan R. , Testa Francine M. , Smith‐Rapaport Susan , Beckerman Barbara , Ebrahimi Nader
Published: March 2003

Summary:  Purpose: Although remission is the ultimate measure of seizure control in epilepsy, and epilepsy syndrome should largely determine this outcome, little is known about the relative importance of syndrome versus other factors traditionally examined as predictors of remission or of relapse after remission. The purpose of this study was to examine remission and relapse with respect to the epilepsy syndrome and other factors traditionally considered with respect to seizure outcome.

Methods: A prospectively identified cohort of 613 children with newly diagnosed epilepsy was assembled and is actively being followed to determine seizure outcomes. Epilepsy syndrome and etiology were classified at diagnosis and again 2 years later. Remission was defined as 2 years completely seizure‐free, and relapse as the recurrence of seizures after remission. Multivariable analysis was performed with the Cox proportional hazards model.

Results: Five hundred ninety‐four of the original 613 children were followed ≥2 years (median follow‐up, 5 years). Remission occurred in 442 (74%), of whom 107 (24%) relapsed. On multivariable analysis, idiopathic generalized syndromes and age at onset between 5 and 9 years were associated with a substantially increased remission rate, whereas remote symptomatic etiology, family history of epilepsy, seizure frequency, and slowing on the initial EEG were associated with a decreased likelihood of attaining remission. Young onset age (<1 year) and seizure type were not important after adjustment for these predictors. Relapses occurred more often in association with focal slowing on the initial EEG and with juvenile myoclonic epilepsy. Benign rolandic epilepsy and age at onset <1 year were associated with markedly lower risks of relapse. About one fourth of relapses were apparently spontaneous while the child was taking medication with good compliance, and more than half occurred in children who were tapering or had fully stopped medication.

Conclusions: A large proportion of children with epilepsy remit. Symptomatic etiology, family history, EEG slowing, and initial seizure frequency negatively influence, and age 5–9 years and idiopathic generalized epilepsy positively influence the probability of entering remission. Factors that most influence relapse tend to be different from those that influence remission.
Magnetic Resonance Spectroscopic Studies of Neurotransmitters and Energy Metabolism in Epilepsy
Authors: Petroff Ognen A. C. , Pan Jullie W. , Rothman Douglas L.
Published: March 2003

Summary: The application of magnetic resonance spectroscopy (MRS) to study brain glutamate and γ‐aminobutyric acid (GABA) metabolism and the coupling of neurotransmitter cycling to neuroenergetics has provided several new, and controversial, insights into the relationship of brain metabolism and function in humans and animal models. Contrary to the previous view of separate metabolic and neurotransmitter pools of glutamate, the glutamate–glutamine cycle has been shown to be a major metabolic pathway tightly coupled to cerebral electrical activity and glucose metabolism. The glycogen‐shunt model provides a mechanistic explanation for the uncoupling of glucose consumption and oxidation during enhanced cerebral electrical activity. A ketogenic diet improves the cerebral energy state of patients with refractory epilepsy. Ketones may act by providing oxidative fuel for non–neurotransmission‐linked cerebral energy needs. This resulting sparing effect on glucose essentially provides an extra source of substrate to eliminate synaptic glutamate, which ultimately reduces excitability. Postictal glutamate reuptake is threefold slower in the gliotic yet epileptogenic human hippocampus, suggesting partial dysfunction of the glia, slowing the glutamate–glutamine cycle. Glutamate and GABA metabolism are coupled at the metabolic and functional levels. GABAergic neurons are dependent on glia to provide glutamine for GABA synthesis (GABA–glutamine cycle). Occipital GABA levels are below normal in many patients with refractory complex partial seizures and juvenile myoclonic epilepsy. Patients with lower GABA levels have slower rates of GABA synthesis. In the human visual cortex, GABA concentrations, and therefore rates of GABA synthesis, appear to be coupled to functional activity and inversely related to cortical excitability. Studies of glutamate/GABA/glutamine cycles, ketone body metabolism, and functional neuroenergetics should provide further insight into the metabolic mechanisms controlling cerebral excitability.
Dynamic Susceptibility Contrast (DSC) MRI and Interictal Epileptiform Activity in Cryptogenic Partial Epilepsy
Authors: Placidi Fabio , Floris Roberto , Bozzao Alessandro , Romigi Andrea , Tombini Mario , Baviera Maria Elena , Sperli Francesca , Izzi Francesca , Mattia Donatella , Marciani Maria Grazia
Published: March 2003

Summary:  Purpose: To study the possible correlation between interictal EEG patterns and neuroradiologic data obtained by dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) in patients with partial epilepsy.

Methods: Seventeen subjects with cryptogenic partial epilepsy underwent long‐term video‐EEG monitoring and DSC‐MRI in the same session. Ten patients had temporal lobe epilepsy (TLE) and seven, epilepsy of extratemporal origin (ExTE). MRI data were compared with EEG findings, and the accuracy of DSC‐MRI was analyzed considering spiking rate (number of interictal epileptiform abnormalities, IEA/min) and type of epilepsy.

Results: DSC‐MRI showed a relevant asymmetry in the frontal, temporal, and occipital regions in eight (47%) of 17 patients, consisting of a relative regional cerebral blood volume (rCBV) increase in these areas. Because this region corresponded to the interictal EEG focus (IEF) or to the hemisphere involved in the genesis of epileptic discharges in most patients showing a higher spiking rate, patients were classified in two groups: patients with high spiking rate (HSR, n = 9) and with low spiking rate (LSR, n = 8); the cutoff corresponded to the median value of IEA/min. The rCBV increase corresponded to the IEF or to the hemisphere involved in the genesis of epileptic discharges in seven (77.7%) of nine HSR patients. No patients with LSR showed significant asymmetries in rCBV pattern. In five of six patients with TLE‐HSR (83.3%), DSC‐MRI showed a relative rCBV increase concordant with IEF or hemisphere involved in the genesis of epileptic discharges; in patients with ExTE‐HSR, the concordance was 66%.

Conclusions: DSC‐MRI is a noninvasive procedure that may provide useful additional information to lateralize and/or localize the IEF when interictal epileptiform activity is sufficiently elevated.
Systemic Overexpression of the α1B‐Adrenergic Receptor in Mice: An Animal Model of Epilepsy
Authors: Kunieda Takeharu , Zuscik Michael J. , Boongird Atthaporn , Perez Dianne M. , Lüders Hans O. , Najm Imad M.
Published: March 2003

Summary:  Purpose: A lack of selective α1‐adrenergic receptor (α1‐ARs) agonists and antagonists has made it difficult to clarify the precise function of these receptors in the CNS. We recently generated transgenic mice that overexpress either wild‐type or a constitutively active mutant α1B‐AR in tissues that normally express the receptor. Both wild‐type and mutant mice showed an age‐progressive neurodegeneration with locomotor impairment and probable stress‐induced motor events, which can be partially reversed by α1‐AR antagonists. We hypothesized that the wild‐type and mutant mice may exhibit spontaneous epileptogenicity as compared with normal (nontransgenic) mice.

Methods: Normal, wild‐type, and mutant mice were studied. Twenty mice (1 year old) underwent prolonged video‐EEG monitoring over a 4‐week period. Raw EEG data were blindly analyzed by visual inspection for the presence of interictal and ictal epileptic activities.

Results: During the acute postoperative period (≤3 days), both wild‐type (26.1 ± 8.07 spikes/day) and mutant mice (116.87 ± 55.13) exhibited more frequent interictal spikes than did normal mice (2.17 ± 0.75; p value, <0.05), but all three groups showed EEG and clinical seizures. During the later monitoring periods (>3 days), wild‐type and mutant mice showed more frequent interictal spikes (15.44 ± 4.07; p < 0.01; and 6.05 ± 2.46; p < 0.05, respectively) as compared with normal mice (0.41 ± 0.41), but only mutant mice had spontaneous clinical seizures (means ± SEM).

Conclusions: The selective overexpression of the α1B‐AR is associated with increased in vivo spontaneous interictal epileptogenicity and EEG/behavioral seizures. These results suggest a possible role (direct or indirect) for the α1B‐ARs in the development and expression of epileptogenicity.
Cerebral Activation during Vagus Nerve Stimulation: A Functional MR Study
Authors: Narayanan Jaishree T. , Watts Richard , Haddad Naim , Labar Douglas R. , Li P. Mark , Filippi Christopher G.
Published: March 2003

Summary:  Purpose: To study the short‐term effects of vagus nerve stimulation (VNS) on brain activation and cerebral blood flow by using functional magnetic resonance imaging (fMRI).

Methods: Five patients (three women, two men; mean age, 35.4 years) who were treated for medically refractory epilepsy with VNS, underwent fMRI. All patients had a nonfocal brain MRI. The VNS was set at 30 Hz, 0.5–2.0 mA for intervals of activation of 30 s on and 30 s off, during which the fMRI was performed. Statistical parametric mapping (SPM) was used to determine significant areas of activation or inhibition during vagal nerve stimulation (p < 0.05).

Results: VNS‐induced activation was detected in the thalami bilaterally (left more than right), insular cortices bilaterally, ipsilateral basal ganglia and postcentral gyri, right posterior superior temporal gyrus, and inferomedial occipital gyri (left more than right). The most robust activation was seen in the thalami (left more than right) and insular cortices.

Conclusions: VNS‐induced thalamic and insular cortical activation during fMRI suggests that these areas may play a role in modulating cerebral cortical activity, and the observed decrease in seizure frequency in patients who are given VNS may be a consequence of this increased activation.
Brain Sterols in the AY‐9944 Rat Model of Atypical Absence Seizures
Authors: Cortez Miguel A. , Cunnane Stephen C. , Snead O. Carter
Published: March 2003

Summary:  Purpose: The AY‐9944 (AY)‐treated rat is a reproducible and clinically relevant animal model of atypical absence seizures. AY inhibits cholesterol synthesis, but the relation between brain sterol levels and the spontaneously recurrent absence seizures has not been determined.

Methods: Long–Evans hooded rats were treated every 6 days from postnatal day (P)2 to P20 with AY (7.5 mg/kg, s.c.) or saline. Electrodes were permanently implanted under pentobarbital anesthesia at P50. Spike‐and‐wave discharge (SWD) duration and amplitude were quantified at P55. Changes in brain sterols after AY were examined in three different experiments, looking at brain regions (experiment 1), recovery after stopping AY (experiment 2), or gender differences (experiment 3).

Results: Experiment 1: AY caused spontaneously recurrent slow SWD that lasted 59 times longer and had a 3.2‐fold higher amplitude than that in controls. At P55, brain cholesterol was reduced and 7‐dehydrocholesterol was increased in all brain regions (p < 0.0001). Experiment 2: Four hundred days after stopping AY‐9944 treatment (P420), brain sterol levels had returned to normal levels, but the AY‐induced SWD lasted twice as long as at P55. Experiment 3: At P55, AY‐induced changes in plasma and liver (but not brain) sterols were significantly more severe in females compared with males.

Conclusions: AY‐induced seizures appear to be related to AY‐induced changes in brain sterols but persisted long after the sterols had returned to normal after the last AY injection. Hence, there appears to be a critical developmental window during which the AY must be given but after which the AY‐induced change in brain sterols is no longer essential to sustaining the seizures.
Effect of Levetiracetam on Epileptiform Discharges in Human Neocortical Slices
Authors: Gorji Ali , Höhling Jorg‐Michael , Madeja Michael , Straub Heidrun , Köhling Rüdiger , Tuxhorn Ingrid , Ebner Alois , Wolf Peter , Panneck H. W. , Behne F. , Lahl Rainer , Speckmann Erwin‐Joseph
Published: March 2003

Summary:  Purpose: The anticonvulsant effects of the novel antiepileptic drug (AED) levetiracetam (LEV) were tested in neocortical slice preparations from 23 patients who underwent surgery for the treatment of refractory epilepsy.

Methods: Slices were used to evaluate the effects of LEV on two different models of epilepsy: low‐Mg2+–induced untriggered and bicuculline‐evoked stimulus‐triggered epileptiform burst discharges and spontaneously appearing rhythmic sharp waves.

Results: LEV (0.1–1 mM) did not influence spontaneously appearing rhythmic sharp waves or Mg2+‐free aCSF‐induced epileptiform field potentials. LEV affected neither the amplitudes or duration nor the repetition rates of burst discharges in these epilepsy models. However, LEV (100–500 μM) significantly suppressed the ictal‐like discharges elicited by the γ‐aminobutyric acid subtype A (GABAA)‐receptor antagonist bicuculline. A marked reduction of the amplitude and duration of bicuculline‐evoked field response in the presence of LEV was observed.

Conclusions: The results indicate the potential for LEV to inhibit epileptiform burst discharges in human neocortical tissue, which is consistent with its effects in animal models of epilepsy. These results also support the seizure reduction observed in clinical trials and support that this may, in part, be related to the ability of LEV to inhibit epileptiform discharges.
Digital Photography and 3D MRI–based Multimodal Imaging for Individualized Planning of Resective Neocortical Epilepsy Surgery
Authors: Wellmer Jörg , Von Oertzen Joachim , Schaller Carlo , Urbach Horst , König Roy , Widman Guido , Van Roost Dirk , Elger Christian E.
Published: March 2003

Summary:  Purpose: Invasive presurgical work up of pharmacoresistant epilepsies presumes integration of multiple diagnostic modalities into a comprehensive picture of seizure onset and eloquent brain areas. During resection, reliable transfer of evaluation results to the patient's individual anatomy must be made. We investigated the value of digital photography–based grid localization in combination with preoperative three‐dimensional (3D) magnetic resonance imaging (MRI) for clinical routine.

Methods: Digital photographs of the exposed cortex were taken before and after grid placement. Location of electrode contacts on the cortex was identified and schematically indicated on native cortex prints. Accordingly, transfer of contact positions to a 3D MRI brain‐surface rendering was carried out manually by using the rendering software. Results of the electrophysiologic evaluation were transferred to either electrode contact reproduction and co‐registered with imaging‐based techniques such as single‐photon emission computed tomography (SPECT), positron emission tomography (PET), and functional MRI (fMRI).

Results: Digital photography allows precise and highly realistic documentation of electrode contact positions on the individual neocortical surface. Lesions underneath grids can be highlighted by semitransparent MRI surface rendering, and lobar boundaries can be identified. Because of integrating electrode contact positions into the postprocessed 3D MRI data set, imaging‐based techniques can be codisplayed with the results of the electrophysiologic evaluation. Comparison with CT/MRI co‐registration showed good accuracy of the method. However, grids not sewn to the dura at implantation can become subject to significant displacement.

Conclusions: Digital photography in combination with preimplantation 3D MRI allows the generation of reliable tailored resection plans in neocortical epilepsy surgery. The method enhances surgical safety and confidence.
Four New Families with Autosomal Dominant Partial Epilepsy with Auditory Features: Clinical Description and Linkage to Chromosome 10q24
Authors: Winawer Melodie R. , Boneschi Filippo Martinelli , Barker‐Cummings Christie , Lee Joseph H. , Liu Jianjun , Mekios Constantine , Gilliam T. Conrad , Pedley Timothy A. , Hauser W. Allen , Ottman Ruth
Published: March 2003

Summary:  Purpose: Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a rare form of nonprogressive lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. The gene predisposing to this syndrome was localized to a 10‐cM region on chromosome 10q24. We assessed clinical features and linkage evidence in four newly ascertained families with ADPEAF, to refine the clinical phenotype and confirm the genetic localization.

Methods: We genotyped 41 individuals at seven microsatellite markers spanning the previously defined 10‐cM minimal genetic region. We conducted two‐point linkage analysis with the ANALYZE computer package, and multipoint parametric and nonparametric linkage analyses as implemented in GENEHUNTER2.

Results: In the four families, the number of individuals with idiopathic epilepsy ranged from three to nine. Epilepsy was focal in all of those with idiopathic epilepsy who could be classified. The proportion with auditory symptoms ranged from 67 to 100%. Other ictal symptoms also were reported; of these, sensory symptoms were most common. Linkage analysis showed a maximum 2‐point LOD score of 1.86 at (θ = 0.0 for marker D10S603, and a maximum multipoint LOD score of 2.93.

Conclusions: These findings provide strong confirmation of linkage of a gene causing ADPEAF to chromosome 10q24. The results suggest that the susceptibility gene has a differential effect on the lateral temporal lobe, thereby producing the characteristic clinical features described here. Molecular studies aimed at the identification of the causative gene are underway.
Molecular Genetics of Human Familial Epilepsy Syndromes
Authors: Hirose Shinichi , Okada Motohiro , Kaneko Sunao , Mitsudome Akihisa
Published: March 2003

Summary: Genetic defects have been recently identified in certain inherited epilepsy syndromes in which the phenotypes are similar to those of common idiopathic epilepsies. Mutations in the neuronal nicotinic acetylcholine receptor α4 and β2 subunit genes have been detected in families with autosomal dominant nocturnal frontal lobe epilepsy. Both receptors are components of neuronal acetylcholine receptor, a ligand‐gated ion channel in the brain. Furthermore, mutations of two K+ channel genes also were identified as the underlying genetic abnormalities of benign familial neonatal convulsions. Mutations in the voltage‐gated Na+‐channel α1 and β1 subunit genes were found as the cause of generalized epilepsy with febrile seizures plus, a clinical subset of febrile convulsions. Mutation of a voltage‐gated K+‐channel gene can cause partial seizures associated with periodic ataxia type 1 and some forms of juvenile myoclonic epilepsy can result from mutations of a Ca2+ channel. This line of evidence suggests the involvement of channels expressed in the brain in the pathogenesis of certain types of epilepsy. Our working hypothesis is to view certain idiopathic epilepsies as disorders of ion channels (i.e., “channelopathies”). Such a hypothesis should provide a new insight into our understanding of the genetic background of epilepsy.
Current Status of Surgery in the Management of Epilepsy
Authors: Shaefi Shahzad , Harkness William
Published: March 2003

Summary:  Purpose: To review systematically the available evidence with regard to the current status of epilepsy surgery in the management of patients with epilepsy.

Methods: A careful search of published literature, including Medline, published reviews, chapters, and cross‐references thereof.

Results: With medical treatment of epilepsy being unsuccessful in many cases, the importance of surgical approaches cannot be underscored. Early surgery is the treatment of choice for patients with clear‐cut mesial temporal sclerosis and results in significant clinical improvement in up to 80% of cases, provided the EEG, neuropsychological, and neuropsychiatric results are in concordance with this approach. In patients with poorly defined, widespread, or dual pathology, however, invasive recordings may be necessary, and while this is performed in major centres, the outcome is rather more variable in this group. Improved surgical techniques, and the use of stereotactic approaches and image guidance procedures, have resulted in surgical resections becoming more selective. With isolated structural lesions such as dysembryoplastic tumours, low‐grade astrocytomas, or focal vascular abnormalities, total macroscopic and radiological evidence of lesional excision is associated with excellent seizure‐free outcome. The first randomised controlled trial of epilepsy surgery has demonstrated clearly the efficacy of these techniques, and the risk of complications.

Discussion: Increasing sophistication of noninvasive presurgical evaluation enables surgical candidates to be identified at an earlier stage and presents a realistic alternative to medical treatment in many cases. The introduction of minimally invasive techniques has had a significant impact on surgical practice and its associated morbidity. The future of epilepsy surgery lies with continued basic science research and its application to clinical medicine.
Identifizierung von Hochrisikopatienten bei schwerer, aber symptomfreier Aortenstenose
Authors: Rosenhek R. , Binder T. , Porenta G. , Lang I. , Christ G. , Schemper M. , Maurer G. , Baumgartner H.
Published: March 2003

Zusammenfassung: Der Nutzen einer Operation bei noch symptomfreier höhergradiger Aortenstenose wird nach wie vor kontroversiell beurteilt. Wir berichten unsere kürzlich im New England Journal of Medicine publizierten Daten zum natürlichen Verlauf dieser Erkrankung und möglichen Prognosefaktoren. 128 konsekutive, asymptomatische Patienten mit höhergradiger Aortenstenose (Alter 60 ± 18 Jahre, maximale Aortenflußgeschwindigkeit 5,0 ± 0,6 m/s), die im Laufe des Jahres 1994 untersucht wurden, wurden anschließend prospektiv bis 1998 weiter beobachtet.  Bei einem mittleren Beobachtungszeitraum von 22 ± 18 Monaten war das ereignisfreie Überleben mit den definierten Endpunkten Tod oder Klappenoperation wegen der Entwicklung von Beschwerden nach einem Jahr 67 ± 5 %, nach 2 Jahren 56 ± 5 % und nach 4 Jahren 33 ± 5 %. 8 Patienten verstarben, davon 6 an kardialer Ursache und 59 Patienten wurden operiert. Die multivariate Analyse zeigte, dass lediglich das Ausmaß der Klappenverkalkung ein unabhängiger Prognosefaktor war, nicht aber das Alter, das Geschlecht oder das Vorhandensein von koronarer Herzkrankheit, Hypertonie, Diabetes mellitus oder Hypercholesterinämie. Bei Patienten mit nicht oder nur leicht verkalkter Aortenklappe betrugen die ereignisfreien Überlebensraten 92 ± 5 % nach einem, 84 ± 8 % nach zwei und 75 ± 9 % nach 4 Jahren. Im Vergleich dazu hatten die Patienten mit mittel‐ oder höhergradiger Verkalkung der Aortenklappe ein ereignisfreies Überleben von 60 ± 6 % nach einem, 47 ± 6 % nach zwei und 20 ± 5 % nach vier Jahren. Eine Hochrisikogruppe stellten jene Patienten dar, die eine mittel‐ oder höhergradig verkalkte Aortenklappe hatten und bei denen zusätzlich ein Anstieg der Aortenflussgeschwindigkeit von über 0,3 m /s innerhalb eines Jahres beobachtet wurde. Innerhalb von 2 Jahren ab dieser Beobachtung wurden 79 % dieser Patienten entweder wegen der Entwicklung von Beschwerden operiert oder sie verstarben.  Zusammenfassend erscheint eine mittel‐ oder höhergradige Klappenverkalkung zusammen mit der Beobachtung einer raschen hämodynamischen Progression eine Hochrisikogruppe von Patienten mit schwerer, noch symptomfreier Aortenstenose zu identifizieren, bei der ein elektiver Klappenersatz in Betracht gezogen werden sollte, anstatt die Entwicklung von Beschwerden abzuwarten.
Bone Mineral Density in Multiple Myeloma  Patients after Intravenous Clodronate Therapy
Authors: Tomíška M. , Adam Z. , Prokeš B. , Dušek L. , Hájek R. , Vorlíček J.
Published: March 2003

Summary: Bisphosphonates inhibit osteoclastic bone destruction that may be stimulated by myeloma cells. By this way, ­bisphosphonates carry the potential to lower the number of new pathological fractures, of hypercalcaemic events, and of intensity of bone pain as was published earlier. Clodronate has been administered orally in most clinical studies so far despite of its poor bio­availability from the gastrointestinal tract.  The aim of our study was to evaluate bone mineral density (BMD) changes in 34 newly diagnosed multiple myeloma patients regularly treated by 900 mg of clodronate in slow intravenous infusions on an outpatient basis in two‐week intervals for at least 24 months. BMD was evaluated by CT scanning every six months. Initial values of trabecular BMD were only about 60 per cent of age‐ and sex‐adjusted healthy population values. Clodronate therapy seemed to preserve BMD within the period of two or three years. This effect was seen not only in patients responding to chemotherapy but even in the small subgroup of patients with persisting active disease.  We conclude that the long‐term intravenous clodronate therapy may contribute to the preservation of BMD and thus calcium hydroxyapatite in bones in multiple myeloma patients concomitantly treated by chemotherapy. The administration of clodronate should start early in the course of disease, before BMD has been markedly reduced.
Verschreibungs‐ und Aufklärungspraxis  bei BenzodiazepinkonsumentInnen
Authors: Gutiérrez‐Lobos Karin , Fröhlich Sabine , Quiner Sylvia , Haring Ch. , Barnas Ch.
Published: March 2003

Zusammenfassung: Der hohe Anteil an Tranquilizer‐LangzeitkonsumentInnen gibt – wegen der daraus resultierenden somatischen und kognitiven Nebenwirkungen, Wechselwirkungen mit anderen Medikamenten sowie Alkohol und der möglichen Beeinträchtigung der Lebensqualität – Anlass zur Sorge. In diesem Zusammenhang wurde in den letzten Jahren die Verschreibungspraxis und die mangelnde Aufklärung der PatientInnen durch ÄrztInnen kritisiert. In dieser Untersuchung gehen wir daher der Frage nach, wie die Verschreibungs‐ und Aufklärungspraxis bezüglich Tranquilizern bei PatientInnen eines Allgemeinkrankenhauses erfolgt. Alle PatientInnen, die im Untersuchungszeitraum an einer Internen Abteilung aufgenommen wurden und einen Tranquilizer verschrieben erhielten, wurden mittels eines semistrukturierten Interviews befragt und nach einem Jahr nachuntersucht. Bei 90 % der späteren AbsetzerInnen und fast 50 % der WeitereinnehmerInnen fand die erstmalige Tranquilizerverschreibung bei Krankenhausaufenthalten statt. Nur 2 % aller PatientInnen bewerteten die Informationen durch den verschreibenden Arzt als ausreichend, 2/3 gaben an, überhaupt keine Information erhalten zu haben. 66 % aller PatientInnen waren über das Abhängigkeitsrisiko informiert, wobei die Aufklärung hauptsächlich durch Apotheken, Beipacktext und Bekannte und nur in etwa 20 % durch ÄrztInnen erfolgte. Richtlinien zur Benzodiazepin‐Verschreibung scheinen sich nur wenig auf die Verschreibungspraxis auszuwirken. ÄrztInnen sollten über die Gefahren der Niedrigdosisabhängigkeit und besonders über komplementäre Therapiemethoden besser geschult werden.
Pathogenese und Klinik hereditärer Nephropathien
Authors: Lhotta K.
Published: March 2003

Zusammenfassung: Hereditäre Erkrankungen spielen in der Differenzialdiagnose von Nephropathien eine nicht unwesent­liche Rolle. Die Niere kann z. B. bei Stoffwechselerkrankungen wie primärer Hyperoxalurie oder M. Fabry betroffen sein. Hereditäre Störungen der Kontrolle von Blutgerinnung oder Komplement können zum hämolytisch‐urämischen Syndrom führen. Eine zentrale Gruppe hereditärer Nephropathien stellen die polyzystischen Nierenerkrankungen dar, allen voran die autosomal dominante polyzystische Nierendegeneration. Vererbte Formen des nephrotischen Syndroms sind durch Störungen der Podozytenfunktion verursacht. Die klassische hereditäre Erkrankung der Basalmembran ist das Alport‐Syndrom. Besonders interessant sind angeborene Störungen der tubulären Transportfunktion. Im speziellen wird auf hereditäre Störungen der Natriumrückresorption eingegangen.
Endokrine Orbitopathie – Diagnostik
Authors: Langmann Andrea , Lindner S.
Published: March 2003

Zusammenfassung: Zur Klassifikation der endokrinen Orbitopathie wird in unterschiedlich modifizierter Form die Klassifika­tion nach Werner (1969), das sogenannte NOSPECS‐Schema herangezogen, dessen Anwendung im Folgenden anhand der Symptomatik der Patienten dargestellt wird.
Interaktionen von Fibroblasten, Adipozyten und immunkompetenten Zellen in der Pathogenese der endokrinen Orbitopathie
Authors: Heufelder A. E.
Published: March 2003

Zusammenfassung: Die Immunthyreopathie vom Typ Morbus Basedow ist Folge eines systemischen Autoimmunprozesses, der bei schwerer Ausprägung neben der Schilddrüse als primärem Zielgewebe auch das in den Orbitahöhlen gelegene Binde‐­, Fett‐ und Augenmuskelgewebe betrifft. Obwohl das primäre Antigen nach wie vor ungewiss ist, dürfte der im Orbitagewebe exprimierte TSH‐Rezeptor – möglicherweise durch „molekulares Mimikry” mit bakteriellen oder viralen Epitopen – eine wesentliche Rolle spielen. Nach Toleranzverlust gegenüber dem endogenen TSH‐Rezeptor kommt eine T‐Zell‐abhängige immunologische Entzündungsreaktion in Gang, die über Zytokine, Interleukine und Prostaglandine zu einer Akkumulation von hydrophilen Glykosaminoglykanen (v. a. Hyaluronsäure, Chondroitinsulfat) im orbitalen Binde‐, Fett‐ und Muskelgewebe führt. Neuen Befunden zufolge spielt auch die gesteigerte Rekrutierung, Differenzierung und Ausreifung von orbitalen Präadipozyten zu Adipozyten und die damit einhergehende Expression des TSH‐Rezeptors eine wichtige Rolle. Folge hiervon ist eine aus­geprägte Volumenzunahme der orbitalen Gewebe mit zunehmender räumlicher Enge in den knöchern begrenzten Orbitae. Durch den intraorbitalen Druckanstieg kommt es als natürliche Form der Druckentlastung zur Protrusio bulbi bei gleichzeitiger Lidretraktion und zu einem schwellungsbedingten Prolaps der entzündlich veränderten Binde‐ und Fettgewebsanteile in die Ober‐ und Unterlider (periorbitale Ödeme). Zusätzlich können Motilitätsstörungen der äußeren Augenmuskeln auftreten, die je nach Ausmaß der asymmetrischen Beeinträchtigung mit Doppelbildern einhergehen. Mit steigender Raumnot entwickeln sich intraorbital zunehmend mechanische Komplikationen, die durch venöse Kongestion, Gewebehypoxie und Bildung von freien Sauerstoffradikalen (Rauchen!) noch verschlimmert werden. Im Extremfall kann die massive Volumenzunahme der Orbita­gewebe zur Expositionskeratitis und Optikusneuropathie führen, die neben den kosmetischen Problemen zu den gravierenden Komplikationen der endokrinen Orbitopathie zählen.
Orbita‐Dekompression bei endokriner Orbitopathie: Vor‐ und Nachteile verschiedener Methoden
Authors: Ettl A.
Published: March 2003

Zusammenfassung: Ausgehend von der Aktivitätsklassifikation nach Mourits werden die Indikationen zur Entlastungsopera­tion der Augenhöhle dargelegt. Danach werden alle modernen Dekompressionsverfahren erwähnt und deren Vor‐ und Nachteile beschrieben. Auch auf die transpalpebrale Fettresektion wird eingegangen. Ergebnisse (Exophthalmusabnahme, Komplikationen) werden für die vom Autor durchgeführten koronalen und transkonjunktivalen Zugänge präsentiert und im Vergleich mit anderen Methoden diskutiert.
Der Stellenwert der Dobutamin‐Streßechokardiographie im Routinebetrieb einer Kardiologischen Abteilung
Authors: Zweng A. , Bachl CH. , Schragel D. , Veegh W. , Schneider Barbara , Stöllberger Claudia
Published: March 2003

Zusammenfassung: Ziel der Studie war die Untersuchung der Rolle der Dobutamin‐Streßechokardiographie (DSE) in einer Abteilung, der etablierte Methoden zur Diagnose und Therapie der koronaren Herzkrankheit (KHK) zur Verfügung stehen.  Zwischen Jänner 1997 und September 1998 wurden 123 Patienten (79 Männer, 44 Frauen, 60,1 ± 9,9 Jahre) zur DSE zugewiesen. Von diesen wurde DSE‐Indikation, ‐Befund und die Konsequenz aus der DSE erfaßt. Nach mindestens einem Jahr wurde ein telefonisches Follow‐up durchgeführt.  Die DSE wurde bei 57 Patienten mit vermuteter und bei 66 Patienten mit bekannter KHK durchgeführt. Indikationen waren inkonklusive Ergometrie oder Myokardszintigraphie (n = 77), Suche nach Hibernation (n = 22), Diskrepanz zwischen Symptomen und Vorbefunden (n = 14) und präoperative Risikostratifizierung (n = 10). In der Gruppe mit vermuteter KHK war der Frauenanteil höher (p = 0,001), umgekehrt verhielt es sich in der Gruppe mit bekannter KHK (p = 0,002). Der DSE‐Befund zeigte neuauftretende Ischämie (n = 35), Hibernation (n = 24), keine neuauftretende Ischämie (n = 56) oder war inkonklusiv (n = 8). Als Konsequenz der DSE wurde 27 Patienten eine invasive Intervention, 10 Patienten eine Revaskularisation, 77 Patienten keine invasive Intervention, 9 Patienten die Operationsfreigabe für eine nicht‐kardiale Operation und einem Patienten eine elektrophysiologische Untersuchung empfohlen. Im untersuchten Zeitraum fanden 955 Ergometrien, 677 Thallium‐Szintigraphien und 987 Koronarangiographien statt. Während des Follow‐up (15 ± 2,9 Monate) verstarben 4 Patienten. Bei 6 Patienten fanden kardiale Interventionen statt. Hinsichtlich DSE‐Befund und Konsequenz gab es keine Unterschiede bei Ereignissen und kardialen Interventionen.  Im Routinebetrieb einer kardiologischen Abteilung spielt die DSE eine Rolle, wenn es um inkonklusive Vorbefunde, Suche nach Hibernation und präoperative Risikostratifizierung geht. Ein negativer DSE‐Befund führt meist zum Verzicht auf eine ­invasive Diagnostik. Wenn der DSE‐Befund positiv ist, spielten bei der Empfehlung zur invasiven Diagnostik zusätzlich die klinische Symptomatik und die Größe des ischämisch reagierenden Myokardareals eine Rolle.
Functional and Health Status Assessment in Patients with Rheumatoid Arthritis
Authors: Stamm Tanja A. , Machold K. P. , Smolen J. S.
Published: March 2003

Summary: Assessing functional and health status in patients with rheumatoid arthritis (RA) can provide information on the individual's functioning in routine occupations and on the individual's well‐being. Data can be obtained by a variety of functional tests and questionnaires. At the Department of Rheumatology at the Vienna University, a specific assessment for outpatients with RA is performed every 3 months. It consists of functional tests, questionnaires, Visual Analog Scales, joint counts, and parameters of disease activity. These data are used to supplement the rheumatologist's decision about medical management of the disease and about further therapeutic strategies.
Long‐term Observation Study of Austrian Patients with Rheumatoid Arthritis
Authors: Skoumal M. , Wottawa A.
Published: March 2003

Summary: We examined retrospectively in a long‐term observation study the outcome of patients with RA in Austria. Eighty‐one inpatients with definite rheumatoid arthritis (RA) completed a standardized clinical and laboratory examination 3 – 8 times between 1978 and 1999. The course of the disease was assessed by determining the disease activity score (DAS), 28‐joint count (28 JC), 30 swollen joint count (30 SJC), proximal interphalangeal joint score (PIP), Ritchie index, Stoke index, Steinbrocker stage, and Larsen score. In a mean duration of follow‐up of 10 years, we observed a statistically significant improvement in PIP, Ritchie index, Stoke index, and DAS. Steinbrocker stage and Larsen score increased significantly. A high percentage of the patients did not receive any disease‐modifying antirheumatic drug (DMARD) within the first 2 years of disease. Of all drugs used, methotrexate (MTX) was continued longer than other DMARDs. The most frequent extra‐articular manifestation was sicca syndrome. In our long‐term follow‐up, a change in treatment from the onset of the disease in the 1980s to a more aggressive treatment within the last decade could be observed. However, with respect to the significant increase in Steinbrocker stage and Larsen score as well, an early aggressive therapy is required. With respect to the association of ANA and extra‐articular manifestations, elevated ANA should give rise to an exact organ screening. For the development of predictive factors for the outcome in patients with RA, it would be helpful to refer patients at risk to specialist care as soon as possible.
18F‐Fluorodeoxyglukose‐Positronenemissionstomographie beim kolorektalen Karzinom: Wertigkeit in Primärstaging und Follow‐up
Authors: Jörg L. , Heinisch M. , Rechberger E. , Kurz F. , Klug R. , Aufschnaiter M. , Hammer J. , Langsteger W.
Published: March 2003

Zusammenfassung: Die Positronenemissionstomographie – mit 18F‐Fluordeoxyglukose – ist ein vielversprechendes bildgebendes Verfahren, das eine sehr sensitive Ganzkörperuntersuchung zur Detektion maligner Herde, die im Vergleich zu gutartigem Gewebe einen erhöhten Glukosestoffwechsel aufweisen, ermöglicht. Es liegen nunmehr einige Studien vor, die den zusätzlichen Wert in Diagnostik und Staging auch beim kolorektalen Karzinom zeigen. Bei insgesamt 20 – 30 % der Patienten, bei denen neben der konventionellen Diagnostik eine Fluordeoxyglukose‐Positronenemissionstomographie durchgeführt wird, dürfte das Management des Patienten zu ändern sein. Die Fluordeoxyglukose‐Positronenemissionstomographie besitzt weiters einen Nutzen in der Kontrolle nach Radio‐ und Chemotherapie. Bezüglich des präoperativen Stagings beim primären kolorektalen Karzinom finden sich in der Literatur bisher keine ausreichenden Daten.
Dynamin Participates in Focal Extracellular Matrix Degradation by Invasive Cells
Authors: Baldassarre Massimiliano , Pompeo Arsenio , Beznoussenko Galina , Castaldi Claudia , Cortellino Salvatore , McNiven Mark A. , Luini Alberto , Buccione Roberto
Published: March 2003

The degradation of extracellular matrix (ECM) by matrix metalloproteases is crucial in physiological and pathological cell invasion alike. Degradation occurs at specific sites where invasive cells make contact with the ECM via specialized plasma membrane protrusions termed invadopodia. Herein, we show that the dynamin 2 (Dyn2), a GTPase implicated in the control of actin-driven cytoskeletal remodeling events and membrane transport, is necessary for focalized matrix degradation at invadopodia. Dynamin was inhibited by using two approaches: 1) expression of dominant negative GTPase-impaired or proline-rich domain-deleted Dyn2 mutants; and 2) inhibition of the dynamin regulator calcineurin by cyclosporin A. In both cases, the number and extension of ECM degradation foci were drastically reduced. To understand the site and mechanism of dynamin action, the cellular structures devoted to ECM degradation were analyzed by correlative confocal light-electron microscopy. Invadopodia were found to be organized into a previously undescribed ECM-degradation structure consisting of a large invagination of the ventral plasma membrane surface in close spatial relationship with the Golgi complex. Dyn2 seemed to be concentrated at invadopodia.
A Dynamin–Cortactin–Arp2/3 Complex Mediates Actin Reorganization in Growth Factor-stimulated Cells
Authors: Krueger Eugene W. , Orth James D. , Cao Hong , McNiven Mark A.
Published: March 2003

The mechanisms by which mammalian cells remodel the actin cytoskeleton in response to motogenic stimuli are complex and a topic of intense study. Dynamin 2 (Dyn2) is a large GTPase that interacts directly with several actin binding proteins, including cortactin. In this study, we demonstrate that Dyn2 and cortactin function to mediate dynamic remodeling of the actin cytoskeleton in response to stimulation with the motogenic growth factor platelet-derived growth factor. On stimulation, Dyn2 and cortactin coassemble into large, circular structures on the dorsal cell surface. These “waves” promote an active reorganization of actin filaments in the anterior cytoplasm and function to disassemble actin stress fibers. Importantly, inhibition of Dyn2 and cortactin function potently blocked the formation of waves and subsequent actin reorganization. These findings demonstrate that cortactin and Dyn2 function together in a supramolecular complex that assembles in response to growth factor stimulation and mediates the remodeling of actin to facilitate lamellipodial protrusion at the leading edge of migrating cells.
Coordination, matching, and wages
Authors: Cao Melanie , Shi Shouyong
Published: March 2003

We analyse the coordination problem in the labour market by endogenizing the matching function and the wage share. Each firm posts a wage to maximize the expected profit, anticipating how the wage affects the expected number of applicants. In equilibrium workers apply to firms with mixed strategies, which generate coordination failure and persistent unemployment. We show how the wage share, unemployment, and the welfare loss from the coordination failure depend on the market tightness and the market size. The welfare loss from the coordination failure is as high as 7.5 per cent of potential output. JEL Classification: C78, J64

Les auteurs analysent le problème de la coordination dans le marché du travail en endogénéisant la fonction 'arrimage et la part des revenus qui va aux salaires. Chaque entreprise définit le niveau de salaire qui maximise ses profits anticipés, en tenant compte de l'effet de ce niveau de salaire sur le nombre des applications qu'elle peut anticiper. De même, les travailleurs font application auprès d'une entreprise à un salaire donné en tenant compte d'une certaine relation d'équivalence entre niveau de salaire et probabilité d'obtenir l'emploi. Voilà qui engendre incoordination et chômage persistant. On montre que la part des revenus qui revient aux salaires, le niveau de chômage, et les pertes de bien‐être attribuables au manque de coordination dépendent de la taille du marché et du degré de rareté de la main d'oeuvre. Les pertes de bien‐être attribuables au manque de coordination correspondent à quelques 7,5 pour‐cent de la production potentielle.
The macroeconomic effects of infrequent information with adjustment costs
Authors: Bonomo Marco , Garcia René
Published: March 2003

We extend the macroeconomic literature on Ss‐type rules by introducing infrequent information in a kinked adjustment‐cost model. We first show that optimal individual decision rules are both state and time dependent. We then develop an aggregation framework to study the macroeconomic implications of such optimal individual decision rules. In our model, a vast number of agents act together, and more so when uncertainty is large. The average effect of an aggregate shock is inversely related to its size and to aggregate uncertainty. These results contrast with those obtained with full information adjustment cost models. JEL Classification: E0,E1,E2,E3

Les effets macroéconomiques de l'information infréquente quand il y a des coûts d'ajustement. Les auteurs étendent la portée de la littérature spécialisée sur les règles de type Ss en proposant des postulats d'information infréquente et de fonction de coûts d'ajustement pliée. On montre que les règles de décision optimales des individus dépendent à la fois de l'état de l'environnement et du moment. On développe alors un cadre d'agrégation pour étudier les impacts macroéconomiques de ces règles optimales de décision. Dans ce modèle, un grand nombre d'agents agissent de concert, et optimales ce d'autant plus que l'incertitude s'accroît. L'effet moyen d'un choc au niveau global est inversement reliéà son importance et au niveau d'incertitude agrégée. Ces résultats contredisent ceux qu'on obtient dans des modèles de coûts d'ajustement avec pleine information.
A dynamic model of endogenous trade policy
Authors: Lapham Beverly , Ware Roger
Published: March 2003

Empirical evidence suggests that past levels of protection are significant determinants of current levels of protection. We investigate dynamic interactions among interest groups and resulting endogenous links between current and future trade policies. We explore these intertemporal links in a small open economy in which lobbying and tariff policies are the outcome of a dynamic game among factor owners. The model can generate cycles with prolonged periods of free trade and/or prolonged periods of restricted trade (i.e., persistent trade policies). An interesting aspect of the environment is the role of lobbying as a partial substitute for intertemporal trade. JEL Classification: F13, C73

Un modèle dynamique de politique commerciale endogène. Les résultats d'analyses empiriques montrent que les niveaux passés de protection sont des facteurs importants dans l'explication des niveaux de protection actuels. Ce mémoire analyse les interactions dynamiques entre groupes d'intérêt et les liens endogènes qui en résultent entre les politiques commerciales présentes et futures. On explore ces liens intertemporels dans une petite économie ouverte où lobbying et politiques tarifaires sont le résultat d'un jeu dynamique entre les propriétaires des facteurs de production. Le modèle peut engendrer des cycles où on observe des périodes prolongées de libre commerce et/ou des périodes prolongées de commerce restreint (i.e. des politiques commerciales persistantes). Il appert que le rôle du lobbying est un substitut partiel pour le commerce intertemporel.
The rank and model specification of demand systems: an empirical analysis using United States microdata
Authors: Nicol Christopher J.
Published: March 2003

A rank‐three demand system is estimated with United States Consumer Expenditure Survey microdata. A unique price data set is also used, which permits the analysis of effects of systematic errors in price variables. It is found that errors in price variables bias test results for the rank‐three hypothesis, in particular towards rejection. Other test results are affected to a lesser extent. Estimating smaller systems of demand equations, even when conditioning on excluded goods, yields significantly different results. Another important conclusion is that model specification is statistically significantly different for households of varying family sizes and housing tenure statuses. JEL Classifications: C31, D12.

Le rang et la spécification du modèle des systèmes de demande: une analyse empirique utilisant des microdonnées américaines. On calibre un système de demande de rang trois à l'aide de microdonnées américaines tirées de la United States Consumer Expenditures Survey. Un ensemble unique de prix est utilisé afin de permettre l'analyse des effets d'erreurs systématiques dans les variables de prix. Il appert que les erreurs dans les variables de prix distorsionnent les résultats du test de l'hypothèse de rang trois en faveur d'un rejet. D'autres résultats de tests sont affectés à un moindre degré. Si l'on calibre de plus petits systèmes d'équations de demande, même en posant des conditions sur des biens exclus, des résultats qui diffèrent de manière significative s'ensuivent. Une autre conclusion importante est que la spécification du modèle est différente de manière statistiquement significative pour les ménages selon la taille de la famille et le statut domiciliaire.