bluuebunny/crossref_metadata_2025 huggingface dataset:
Seizure Clustering during Epilepsy Monitoring
Authors: Haut Sheryl R. , Swick Cynthia , Freeman Katherine , Spencer Susan
Published: March 2003

Summary:  Purpose: To identify risk factors associated with seizure clustering during epilepsy monitoring and to assess the effect of clustering on localization of the epileptogenic zone.

Methods: Patients undergoing presurgical epilepsy monitoring at Montefiore Medical Center or Yale–New Haven Hospital were recruited. Seizure clustering was defined as three or more seizures within 24 h. Risk factors for seizure clustering were examined by using regression analysis. The effect of clustering on localization was examined by Student's t test evaluation of mean interseizure interval for consecutive concordant and discordant seizures.

Results: Of 91 patients, clustering was present in 56 (61.5%). Variables significantly associated with clustering included a history of seizure clustering at home (p = 0.0003) and the presence of mesial temporal sclerosis (MTS) on magnetic resonance imaging (MRI; p = 0.0172). Clustering was present in nine of 10 patients with more than one seizure‐onset zone. Ictal EEG localization was not associated with clustering, nor was rapid medication withdrawal. Mean interseizure intervals were not significantly different for concordant and discordant seizures.

Conclusions: Seizure clustering during epilepsy monitoring is common. Risk factors include history of clustering at home, MTS on MRI, and possibly more than one seizure focus. In this study, seizures that occurred in clusters had as important a role in localization as did nonclustered seizures.
Clinical and Electrographic Features of Epileptic Spasms Persisting Beyond the Second Year of Life
Authors: De Menezes Márcio A. Sotero , Rho Jong M.
Published: March 2003

Summary:  Purpose: Few reports detailing the electroclinical features of epileptic spasms persisting beyond infancy have been published. We sought to characterize this unique population further.

Methods: We retrospectively reviewed the clinical and video‐EEG data on 26 patients (4–17 years; mean, 93 months) with a confirmed diagnosis of epileptic spasms and who were evaluated at our tertiary referral center between 1993 and 2000.

Results: In half of our cases, epileptic spasms were associated with disorders of neuronal migration, severe perinatal asphyxia, and genetic anomalies. Interictal EEGs showed generalized slowing in the majority of patients, and a slow‐wave transient followed by an attenuation of the background amplitude was the most common ictal EEG pattern associated with an epileptic spasm (19 cases). Other seizure types (number of cases in parentheses) included tonic seizures with or without a preceding spasm (13), partial seizures (11), myoclonic seizures (11), generalized tonic–clonic seizures (six), atypical absence seizures (two), and atonic seizures (one). Cases with a more organized EEG background (especially with frequencies ≥7 Hz) were more likely to have better cognition. Continued disorganization of the EEG background and persistence of hypsarrhythmia were associated with poor developmental outcome.

Conclusions: Patients with epileptic spasms persisting beyond age 2 years constitute a truly refractory population, one that should be better recognized by clinicians. Interestingly, although many therapies resulted in a >50% reduction in seizures, neither neurocognitive function nor quality of life was substantially improved with intervention. The interictal EEG background is the most helpful in predicting neurologic outcome.
Surgical Implications of Neuromagnetic Spike Localization in Temporal Lobe Epilepsy
Authors: Iwasaki Masaki , Nakasato Nobukazu , Shamoto Hiroshi , Nagamatsu Ken‐ichi , Kanno Akitake , Hatanaka Keisaku , Yoshimoto Takashi
Published: March 2003

Summary:  Purpose: To investigate the clinical usefulness of magnetoencephalography (MEG) as a guide to the surgical treatment of temporal lobe epilepsy (TLE).

Methods: Preoperative spike localization by MEG was compared with seizure outcome and postoperative spike localization at 12 months after resective surgery in 16 patients with TLE. Spike localization was classified into anterior temporal (AT) and non‐AT localization in 11 patients without neocortical lesion treated with anterior temporal lobectomy (ATL); and lesion and lobar localization in five patients with neocortical lesion treated with lesionectomy (n = 3) or lesionectomy with medial temporal resection (n = 2).

Results: All five patients with AT localization became seizure free and spike free after surgery. Among the six patients with non‐AT localization, two became seizure free and spike free, two became seizure free with residual spikes, one had residual seizures but no spikes, and one had both residual seizures and spikes. All three patients with lesion localization and two with lobar localization had favorable seizure outcome and became spike free after surgery.

Conclusions: MEG spike localization can identify neocortical sources remote from the presumed epileptogenic area. Favorable seizure outcome can be expected in patients with AT localization after ATL and patients with lesion localization after lesionectomy. In contrast, non‐AT localization indicates either nonmedial TLE or spike propagation to the posterior and extratemporal neocortex. Similarly, lobar localization indicates spike propagation from an epileptogenic lesion or extensive epileptogenicity. Patients with non‐AT localization or lobar localization should undergo intensive evaluations, such as intracranial EEG, for improved seizure outcome.
Iron Status: A Possible Risk Factor for the First Febrile Seizure
Authors: Daoud Azhar S. , Batieha Anwar , Abu‐Ekteish Faisel , Gharaibeh Nayef , Ajlouni Saleh , Hijazi Saad
Published: March 2003

Summary:  Purpose: We conducted a controlled study to investigate the relation of iron status and first febrile seizure (FFS).

Methods: Measures of iron sufficiency including hemoglobin concentration (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and plasma ferritin (PF) were prospectively measured in 75 children with FFS and compared with 75 controls matched for age and sex with febrile illnesses without convulsions.

Results: Mean ferritin level was significantly lower in cases with FFS (29.5 ± 21.3 μg/L) than in controls (53.3 ± 37.6 μg/L) with p = 0.0001. The proportion of subjects with a PF level ≤30 μg/L was significantly higher among children with FFS (49 of 75 vs. 24 of 75) than in controls (p = 0.000). Mean levels of HB, MCV, and MCH also were lower among FFS cases, but differences failed to attain statistical significance. A higher proportion of cases with FFS had an HB <110 g/L, MCV <72 fL, and MCH <24 pg than did the controls, but the differences were not statistically significant. There were no statistically significant differences between the cases and the controls in the mean peak temperature on admission, types of underlying illness, or family history of epilepsy and of febrile convulsion.

Conclusions: PF level was significantly lower in children with FFS than in the reference group, suggesting a possible role for iron insufficiency in FFS.
Glutamate–glutamine Cycling in the Epileptic Human Hippocampus
Authors: Petroff Ognen A. C. , Errante Laura D. , Rothman Douglas L. , Kim Jung H. , Spencer Dennis D.
Published: March 2003

Summary:  Purpose: Several findings suggest that energy metabolism and the glutamate–glutamine cycle may be impaired in epilepsy. Positron emission tomography often shows interictal hypometabolism of the epileptogenic hippocampus. In vivo microdialysis studies show that seizure‐associated glutamate release is doubled, and clearance is slowed. We hypothesized that the glutamate–glutamine cycle between neurons and glia may be decreased in the epileptic human hippocampus.

Methods: A 20% solution of 2‐13C‐glucose was infused before resection of the epileptogenic hippocampus. Blood glucose isotopic fractions were measured every 30 min. Blood and brain specimens were frozen quickly; perchloric acid extracts of the small metabolites were prepared and analyzed by proton and carbon magnetic resonance spectroscopy (MRS) at 11.75 Tesla.

Results: Standard histology showed 12 with hippocampal sclerosis and five with minimal neuron loss. The relative rates of glutamate–glutamine cycling with respect to glutamate synthesis were decreased in biopsies affected by hippocampal sclerosis (mean, 0.08; 95% confidence interval, 0.04–0.12) compared with those with minimal neuron loss (0.52; 95% CI, 0.30–0.75). Mean cellular glutamate concentrations were higher in minimal neuron loss (8.9 mM; 95% CI, 7.4–10.4) than hippocampal sclerosis (7.3 mM; 95% CI, 5.9–8.7). Cellular glutamine concentrations (mean, 2.8 mM; 95% CI, 2.4–3.2; n = 17) were the same in all groups.

Conclusions: The epileptogenic, gliotic human hippocampus appears to be characterized metabolically by slow rates of glutamate–glutamine cycling, decreased glutamine content, and a relative increase in glutamate content. We hypothesize that the low rate of glutamate–glutamine cycling that results from a failure of glial glutamate detoxification could account for slow glutamate clearance from synapses and continuing low‐grade excitotoxicity.
Ictal Vomiting in Association with Left Temporal Lobe Seizures in a Left Hemisphere Language–Dominant Patient
Authors: Schäuble Barbara , Britton Jeffrey W. , Mullan Brian P. , Watson James , Sharbrough Frank W. , Marsh W. Richard
Published: March 2003

Summary: Ictal vomiting is considered a localizing sign indicating nondominant lateralization in patients with partial seizures of temporal lobe origin. We report a case of ictal vomiting associated with left temporal seizure activity in a left hemisphere language–dominant patient with a left mesial temporal glioma. Bilateral mesial temporal depth electrodes helped verify seizure lateralization. Surgery consisting of tumor resection and a left anterior temporal lobectomy and amygdalohippocampectomy resulted in freedom from seizures and episodes of vomiting. This case indicates that ictal vomiting can occur as a manifestation of left temporal onset seizures in left hemisphere–dominant patients.
Brain Diffusion after Single Seizures
Authors: Hufnagel Andreas , Weber Johannes , Marks Sonja , Ludwig Tanja , De Greiff Armin , Leonhardt Georg , Widmann Guido , Stolke Dietmar , Forsting Michael
Published: March 2003

Summary:  Purpose: Diffusion‐weighted magnetic resonance imaging (DWI) after focal status epilepticus has demonstrated focal alterations of the apparent diffusion coefficient (ADC) in the epileptogenic zone. We hypothesized that localized dynamic alterations of brain diffusion during the immediate postictal state will be detectable by serial DWI and correlate with the epileptogenic zone.

Methods: Nine adult patients (four men, five women) with medically intractable epilepsy were prospectively examined with a total of 25 DWI scans taken 2–210 min after a seizure.

Results: The interictal ADC was significantly (p < 0.05) elevated in the ictogenic hippocampus in all patients with temporal lobe epilepsy. The following postictal changes of the ADC were seen: (a) decreases by maximally 25–31%, which were most pronounced in the epileptogenic zone (n = 2); (b) generalized ADC changes after generalized seizures (n = 1) or prolonged complex partial seizures (n = 2); (c) no major changes after short‐lived seizures or if the time to first DWI scan was >15 min or both (n = 3); and (d) widespread bilateral ADC increases after a flumazenil‐induced seizure (n = 1).

Conclusions: ADC changes seen during serial postictal DWI are complex and appear to reflect origin and spread of the preceding seizure. A delineation of the epileptogenic zone appears to be possible only in complex‐partial seizures of >60 s duration that do not secondarily generalize.
Epilepsy‐induced Changes in Signaling Systems of Human and Rat Postsynaptic Densities
Authors: Wyneken Ursula , Marengo Juan‐Jose , Villanueva Sergio , Soto Dagoberto , Sandoval Rodrigo , Gundelfinger Eckart D. , Orrego Fernando
Published: March 2003

Summary:  Purpose: To study seizure‐induced changes in signaling proteins present in postsynaptic densities (PSDs) isolated from human epileptic neocortex and from rat cortex in which seizures were induced by injection of kainic acid.

Methods: We performed Western blot analysis of signaling proteins in PSDs isolated from cortical tissue.

Results: Seizures induce a strong upregulation of TrkB, the receptor for brain‐derived neurotrophic factor (BDNF), whereas components of the N‐methyl‐d‐aspartate (NMDA)‐receptor complex are downregulated in both human and rat PSDs.

Conclusions: These data show that long‐term changes in PSD composition occur as a consequence of epileptic seizure activity.
Quality of Life in Psychogenic Nonepileptic Seizures
Authors: Szaflarski Jerzy P. , Hughes Cynthia , Szaflarski Magdalena , Ficker David M. , Cahill William T. , Li Maureen , Privitera Michael D.
Published: March 2003

Summary:  Purpose: Psychogenic nonepileptic seizures (PNESs) are events that alter or seem to alter the neurologic function and, in their appearance, resemble epileptic seizures (ESs). In patients with ESs the psychological and medical aspects of epilepsy greatly influence the health‐related quality of life (HRQOL). The relation between these factors and PNESs is not well established. In this study, we compared HRQOL in patients with PNESs with that of patients with ESs.

Methods: We evaluated 105 patients admitted to the Epilepsy Monitoring Unit of University Hospital between January 20, 2001, and January 20, 2002. Only patients with the definite diagnosis of ESs or PNESs were analyzed (n = 85). Patients completed an epilepsy‐specific quality‐of‐life instrument (QOLIE‐89), the Profile of Mood States (POMS), and Adverse Events Profile (AEP). We used t tests and regression analyses to contrast HRQOL in PNESs and ESs and to elucidate the main factors associated with HRQOL in patients with PNESs.

Results: In our sample, 45 patients had PNESs, and 40 had ESs. The overall HRQOL and scores on 13 of 19 QOLIE‐89 subscales were significantly lower (i.e., worse) in PNES than in ES patients. AEP and scores on five of six POMS subscales also were worse in PNES patients than in ES patients. PNES versus ES diagnosis, POMS depression/dejection, and AEP were significant predictors of HRQOL, jointly explaining 65% variation in HRQOL. The lower HRQOL in PNESs versus ESs was in part explained by depression and AEP.

Conclusions: Patients with PNESs have a lower HRQOL and worse mood problems than do patients with ESs. This disadvantage is primarily due to depression and medication side effects, although these factors influence QOL in much the same way in PNES and ES patients. These baseline HRQOL data on patients with PNESs can be used to evaluate the effects of treatment in this patient population.
Correlation of Hippocampal Glucose Oxidation Capacity and Interictal FDG‐PET in Temporal Lobe Epilepsy
Authors: Vielhaber Stefan , Von Oertzen Joachim H. , Kudin Alexei F. , Schoenfeld Ariel , Menzel Christian , Biersack Hans‐Juergen , Kral Thomas , Elger Christian E. , Kunz Wolfram S.
Published: March 2003

Summary:  Purpose: Interictal [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) demonstrates temporal hypometabolism in the epileptogenic zone of 60–90% of patients with temporal lobe epilepsy. The pathophysiology of this finding is still unknown. Several studies failed to show a correlation between hippocampal FDG‐PET hypometabolism and neuronal cell loss. Because FDG is metabolized by hexokinase bound to the outer mitochondrial membrane, we correlated the glucose‐oxidation capacity of hippocampal subfields obtained after surgical resection with the corresponding hippocampal presurgical FDG‐PET activity.

Methods: In 16 patients with electrophysiologically confirmed temporal lobe epilepsy, we used high‐resolution respirometry to determine the basal and maximal glucose‐oxidation rates in 400‐μm‐thick hippocampal subfields obtained after dissection of human hippocampal slices into the CA1 and CA3 pyramidal subfields and the dentate gyrus.

Results: We observed a correlation of the FDG‐PET activity with the maximal glucose‐oxidation rate of the CA3 pyramidal subfields (rp = 0.7, p = 0.003) but not for the regions CA1 and dentate gyrus. In accordance with previous studies, no correlation of the FDG‐PET to the neuronal cell density of CA1, CA3, and dentate gyrus was found.

Conclusions: The interictal hippocampal FDG‐PET hypometabolism in patients with temporal lobe epilepsy is correlated to the glucose‐oxidation capacity of the CA3 hippocampal subfield as result of impaired oxidative metabolism.
Adolescent Seizures and Epilepsy Syndromes
Authors: Wheless James W. , Kim Howard L.
Published: March 2003

Summary:Specific epilepsy syndromes begin during adolescence and create a significant neurologic burden. Knowledge of these syndromes has important treatment and prognostic implications, which usually extend into adulthood. Little is known about the effect of menarche on seizures, even though a relationship of seizures to the menstrual cycle has been observed for many years. In general, puberty is not thought to influence seizure frequency. However, estrogen is thought to activate epileptiform activity; testosterone may decrease seizure activity; and progesterone decreases epileptiform discharges. These effects are mediated by effecting γaminobutyric acid (GABA) transmission. Idiopathic generalized epilepsies are the most frequent group with adolescent onset. These are probably polygenic in origin and represent a biologic continuum. Juvenile myoclonic epilepsy (JME) is the most common form. This contrasts with a variety of progressive myoclonic epilepsies that also are first seen in adolescence and have a genetic origin and specific treatments. Finally, although temporal lobe epilepsy associated with hippocampal sclerosis may have its origin in childhood, often the child does not come to surgical evaluation until adolescence or young adulthood. The characteristic clinical history, seizure semiology, and magnetic resonance imaging findings have allowed a discrete epilepsy syndrome to be established. Applying these same criteria to children and adolescents reveals that hippocampal sclerosis is the most common lesion responsible for their intractable temporal lobe epilepsy. Hippocampal sclerosis is probably underdiagnosed in children. The safety and efficacy of epilepsy surgery in the age group is excellent. Knowledge of the epilepsy syndromes that remit before adolescence, may persist into adolescence, or begin in adolescence is central to the treatment of this age group.
Children Versus Adults: Pharmacokinetic and Adverse‐Effect Differences
Authors: Anderson Gail D.
Published: March 2003

Summary: Pharmacokinetic differences may play a part in the age‐related differences in the incidence of adverse effects. The most common idiosyncratic reaction to lamotrigine (LTG) is rash, affecting 10–20% of patients. Risk factors are young age, concurrent valproate (VPA), high starting dose, and rapid escalation. In children, cytochrome P450 (CYP)‐catalyzed metabolism is increased, and uridine diphosphate (UDP)‐glucuronosyltransferase (UGT)‐catalyzed metabolism is not significantly different from that in adults. A CYP‐catalyzed arene oxide intermediate of LTG has been identified. The increase CYP metabolism of LTG in children could result in increased formation of the reactive metabolite and a higher incident of rash. Children often received higher milligram per kilogram doses compared with adults. The higher dose would cause an increased amount of LTG metabolized to the reactive arene oxide intermediate. VPA therapy is associated with a transient elevation in liver‐function tests in 15–30% of patients and a rare, fatal hepatotoxicity. Most cases of VPA hepatotoxicity occurred in children younger than 2 years who had preexisting neurologic or other physical defects. Hypotheses regarding the pathogenesis of the hepatotoxicity include preexisting mitochondrial disease or inborn errors of metabolism, VPA inhibition of β‐oxidation, and toxicity from VPA metabolites VPA, 4‐ene‐VPA, and 2,4‐diene‐VPA. Infants and children have higher concentration ratios of 4‐ene‐VPA to VPA. Polytherapy with enzyme inducers increases the formation of the hepatotoxic metabolites. The role of underlying metabolic disorders associated with hepatodegeneration and intractable seizures without VPA is a major confounder in identifying risk factors and demonstrates the difficulty in separating underlying disease factors in rare idiosyncratic reactions.
Delayed Sclerosis, Neuroprotection, and Limbic Epileptogenesis After Status Epilepticus in the Rat
Authors: Ebert Ulrich , Brandt Claudia , Löscher Wolfgang
Published: March 2003

Summary:  Purpose: Hippocampal sclerosis and massive neurodegeneration in other parts of the limbic system are considered hallmarks of temporal lobe epilepsy. Using the rat model of kainate‐induced status epilepticus, we sought to determine if limbic sclerosis after an excitotoxic insult follows a delayed type of neurodegeneration and is thus accessible to neuroprotective intervention after the insult. Effective pharmacologic neuroprotection after status epilepticus also addresses the old question of whether degenerative morphologic changes after an epilepsy‐inducing event like status epilepticus are the primary cause of epileptogenesis (i.e., the development of recurrent spontaneous seizures) during the following weeks.

Methods: Female Wistar rats after 90 min of generalized status epilepticus were used. Molecular biologic and histologic techniques were used to demonstrate markers of delayed cell death (apoptosis) 48 h after the status. The neuroprotective effects of i.c.v. injections of caspase inhibitors and systemic injections of the anticonvulsant drugs (AEDs) dizocilpine and retigabine after the status epilepticus were studied. The effect of neuroprotective intervention on the development of recurrent spontaneous seizures was investigated by behavioral observation of the rats.

Results: After generalized status epilepticus in Wistar rats, massive sclerosis of the hippocampus and the piriform cortex occurred. TUNEL labeling and electron microscopy revealed that apoptosis is involved in the degenerative processes. Immunohistochemical analysis of the time course of the expression of the proapoptotic protein Bax suggested a maximal induction of apoptosis 24–48 h after the status. Application of caspase inhibitors before or after the status did not reduce lesions, although Bax labeling was reduced. Injection of dizocilpine and to a lower extent also of retigabine after the status prevented limbic neurodegeneration and expression of markers of apoptosis. However, the neuroprotection by dizocilpine did not prevent the development of recurrent spontaneous seizures.

Conclusions: Prolonged seizure activity can induce delayed sclerosis in the hippocampus and other parts of the limbic system. This delayed cell loss can be prevented by neuroprotective drugs after a status epilepticus. However, the damage in limbic brain regions is not the main reason for limbic epileptogenesis and the occurrence of recurrent spontaneous seizures.
The Natural History of Epilepsy in the Era of New Antiepileptic Drugs and Surgical Treatment
Authors: Sander J. W.
Published: March 2003

Summary:  Purpose: To review the factors influencing prognosis of epilepsy in this era of antiepileptic drugs and surgical treatment.

Methods: Systematic review of peer‐reviewed literature.

Results: The prognosis depends on many factors; aetiology, age of onset, number of siezures at onset, the natural history of the condition, and the influence of treatment. However, between 70 and 80% of people developing epilepsy will go into long‐term remission, usually within the first 5 years.

Discussion: Prognosis in epilepsy is the prospect of attaining complete seizure freedom once a pattern of recurrent epileptic seizures has been established. Well‐designed prospective cohort studies using standard outcome measures need to be conducted, especially in non‐Western cultures.
Helicobacter pylori und Magenkarzinom
Authors: Krejs G. J.
Published: March 2003

Ein Reihe von epidemiologischen Studien sowie Zusammenfassungen solcher Studien in Metaanalysen haben einen signfikanten Zusammenhang zwischen Helicobacter pylori‐Infektion der Magenschleimhaut und der Häufigkeit von Magenkrebs gebracht. Das Risiko, bei H. p‐Positiven Krebs zu entwickeln, ist im Durchschnitt etwa 6mal höher als bei Nichtinfizierten. Während in Ländern wie Österreich etwa 1 % der H. p.‐Positiven Magenkrebs in ihrem Leben entwickeln, tritt dies nur bei einem pro 750 Nichtinfizierten ein. Die molekularen Zusammenhängen sind nicht klar, doch dürfte besonders eine Beeinträchtigung des Tumorsuppressorgens p53 eine Rolle spielen. Da die Infektion jedoch häufig ist (etwa 30 % der Gesamtbevölkerung in Österreich) und der Magenkrebs ohne Helicobacter‐Eradikation seltener geworden ist (1997: 24 neue Fälle pro 100 000 Einwohner pro Jahr), wird die Helicobacter‐Eradikation zur Krebsprophylaxe nicht empfohlen. Bei Patienten, die eine positive Familienanamnese in Bezug auf Magenkrebs haben oder bei denen früher ein Magenkrebs reseziert wurde, sollte die H. p.‐Eradikation jedoch aufgrund der Maastrichtempfehlungen durchgeführt werden. Ein Rechenbeispiel wird vorgeführt, dass im Vergleich zu anderen Maßnahmen der Krebsprävention oder Früherkennung, die Kosten von 120 000 ATS pro verhinderten Magenkrebs eine sehr gute Investition bei allgemeiner H. p.‐Eradikation bei über 50jährigen wäre.
Elektromagnetische Felder – Auswirkungen auf die Gesundheit
Authors: Stepansky R. , Jahn O. , Windischbauer G. , Zeitlhofer J.
Published: March 2003

Zusammenfassung: Vorliegende Literaturübersicht zeigt den derzeitigen Wissensstand über gesundheitliche Folgen von statischen und niederfrequenten elektrischen und magnetischen Feldern und von hochfrequenten elektromagnetischen Feldern (bis zu einer Frequenz von 300 GHz) für den Menschen. Zunächst werden die wichtigsten physikalischen Grundkenntnisse und die derzeit gültigen Grenzwertbestimmungen erörtert. Anschließend werden, getrennt für die unterschiedlichen Frequenzbereiche, natürliche und technische Quellen sowie die unterschiedlichen biologischen Auswirkungen mit Schwerpunkt auf potentiell gefährdende Folgen wie Kanzerogenität oder Einfluß auf das Gehirn dargelegt. Offene Fragen und zukünftiger Forschungsbedarf werden dargelegt. Abschließend folgen Betrachtungen über Elektrosensibilität und über psychologische Aspekte.
Praxis der Behandlung koronarer Risikofaktoren bei niedergelassenen Ärzten in Österreich
Authors: Schwarz B. , Hartl H. , Rieder Anita , Kunze M.
Published: March 2003

Zusammenfassung: Die Untersuchung hatte zum Ziel, die Praxis der Prävention koronarer Herzkrankheiten bei österreichischen niedergelassenen praktischen Ärzten und Internisten zu untersuchen. In einer Fragebogenerhebung wurde von 67 praktischen Ärzten und Internisten aus dem Bundesgebiet das Wissen und die Einstellung bezüglich der Primärprävention koronarer Herzkrankheiten mit dem Schwerpunkt Hyperlipidämie erhoben. Als Indikation für eine diätetische Behandlung wurden von 96,6 % der teilnehmenden Ärzte Gesamtcholesterinwerte bis zu 250 mg/dl genannt, als Indikation für Lipidsenker von 98,0 % Gesamtcholesterin‐Werte bis zu 300 mg/dl. Bei den korrespondierenden Werten des Quotienten Gesamt‐ zu HDL‐Cholesterin und besonders des LDL‐Cholesterins war die Häufigkeit der Nennungen geringer. Der durchschnittliche Zeit­aufwand für Patienten mit Hyperlipidämie wurde von 37,9 % mit bis zu 5 Minuten angegeben und von 10,3 % mit mehr als 15 Minuten und war vergleichbar dem Zeitaufwand für übergewichtige Patienten und niedriger als bei Hypertonikern und Diabetikern. Der Behandlungserfolg einer Diättherapie wurde in Bezug auf Hyperlipidämie vergleichbar dem Übergewicht eingeschätzt, aber schlechter als bei Hypertonie oder Diabetes, der Behandlungserfolg der medikamentösen Hyperlipidämietherapie wurde dagegen besser als bei Übergewicht und Diabetes und schlechter als bei Hypertonie eingestuft. Als wichtigste Maßnahmen zur Verbesserung der Präventivmedizin in der Praxis nannten die Ärzte vermehrte Zeitressourcen und ein verbessertes Weiterbildungsprogramm. Die überwiegende Mehrzahl der Ärzte gibt an, dass sich die Versorgungsqualität in den letzten fünf Jahren sowohl im stationären als auch im niedergelassenen Bereich verbessert hat.
The Limits of Surgical Treatment of Non‐Small Cell Lung Cancer
Authors: Skřičková Jana , Špelda S. , Kaplanova Jana
Published: March 2003

Summary: Between January 1, 1991 until December 31, 1996, 286 patients with non‐small cell lung cancer were diagnosed and treated in the Department of Tuberculosis and Respiratory Diseases and Palliative Care Unit in Babice nad Svitavou, Czech Republic. There were 251 (87.8 %) males and 35 (12.2 %) females. The mean age of the whole group was 63.8 years. According to TNM staging (regarding the locoregional extension of the disease) as the only criterion 112 patients (39.2 %) were eligible for surgical resection of primary lung tumour. However lung surgery was performed in 57 patients (19.9 %) with successful radical resection in 49 cases (17.1 %) out of 286. Surgical procedure was contraindicated in 55 (49.1 %) out of 112 potentially resectable patients mostly because of limited cardiopulmonary function. The strategy of neoadjuvant treatment before the resection of lung tumour was used for 12 (4.2 %) patients. Chemotherapy, radiotherapy or the combination of both treatment modalities was used in 121 (42.3 %) patients. Symptomatic therapy alone was chosen in 104 (36.4 %) cases.  The performance of radical resection of lung tumours resulted in a significant influence on the overall survival in the subgroup of all patients with potentially locoregionally operable disease according to the TNM staging. The median survival period reached 17 months if radical resection was done compared to 8.5 months if radical resection was not performed. This difference is statistically significant, p = 0.05.
Hypertonie und chronische Niereninsuffizienz
Authors: Rosenkranz A. R.
Published: March 2003

Zusammenfassung: In den letzten zehn Jahren kam es zu einem kontinuierlichen Anstieg der Inzidenz der Patienten mit chronischer Nierenersatztherapie in Österreich. Ein Rückgang dieser Zahlen wäre vor allem durch eine entsprechende Senkung sowohl des systolischen als auch des diastolischen Blutdrucks möglich. Unabhängig von der Substanzklasse wird jeg­liche antihypertensive Therapie, die effektiv den Blutdruck senkt, die Entwicklung einer Niereninsuffizienz verlangsamen. Wo immer auch möglich, sollten ACE‐Hemmer Teil des Therapieregimes sein, weil bei dieser Substanzgruppe eine Renoprotek­tion über den antihypertensiven Effekt hinaus bei bestimmten Nierenerkrankungen festgestellt wurde. In dieser Arbeit soll ein Überblick über die Pathogenese der Hypertonie bei Patienten mit Niereninsuffizienz gegeben werden; zusätzlich werden Behandlungsstrategien und der Einsatz renoprotektiv wirksamer Antihypertensiva diskutiert.
Stellenwert der Sonographie in der ­Nierentransplantation
Authors: Tiefenthaler M. , Riedl‐Huter Claudia
Published: March 2003

Zusammenfassung: Das bildgebende Verfahren der Wahl nach Nierentransplantation ist der Ultraschall. Neben der fehlenden Strahlenbelastung ist die allgemeine Verfügbarkeit und die hohe Bildauflösung moderner Geräte Grund dafür, dass auf die Sonographie unmittelbar postoperativ nicht mehr verzichtet werden kann. In der Diagnostik der späteren Transplantatdysfunktionen ist die Sonographie ebenso unverzichtbar, wenngleich der Stellenwert in der Abstoßungsdiagnostik weiterhin ­umstritten ist. Mittels farbkodierter Duplexsonographie sind Gefäßverschlüsse, Anastomosenverhältnisse und die Organdurchblutung unblutig messbar und im Verlauf unaufwendig monitorisierbar. Der Stellenwert der neuen Techniken wie 3‐D‐Sonographie, Kontrastmittelduplexsonographie und Harmonic Imaging ist gerade in der Abstoßungsdiagnostik derzeit noch unklar. In diesem Artikel werden Indikationen und Limitierungen der klinischen Praxis der Methode aufgezeigt.
Prognostic Significance of Liver Metastases as First Site of Generalisation in Patients with Breast Cancer – A Retrospective Analysis
Authors: Baur Martina , Schlappack O. , Havelec L. , Wrba F. , Dittrich C.
Published: March 2003

Summary: Of 672 patients with metastatic breast cancer, 24 evaluable patients with primary liver metastases were analysed with regard to their prognostic variables and survival. In 50 % of these patients, liver metastases were found within the first 8.5 months after the diagnosis of breast cancer. The median survival of 10 months (range 0 – 60 + months) was extremely unfavourable. The median survival of hormone‐receptor‐positive patients (11 months) was significantly longer than that of patients with hormone‐receptor‐negative tumours (4 months) (P = 0.025). Patients with elevated lactate dehydrogenase (LDH), glutamic‐oxaloacetic transaminase (GOT) (> 50 U/l), or bilirubin levels at diagnosis had a significantly shorter median survival than patients with normal laboratory parameters (P = 0.001, P = 0.047, and P = 0.056, respectively).  This retrospective study confirms the short survival time for breast cancer patients with liver metastases as initial site of relapse. Hormone‐receptor status and the laboratory parameters LDH, GOT, and bilirubin were identified as important prognostic factors for survival.
Early Clamping of Umbilical Cord Blood and Foetal CD34 Enrichment
Authors: Pafumi C. , Milone G. , Maggi I. , Russo A. , Farina M. , Pernicone G. , Bandiera S. , Giardina P. , Mangiafico L. , Mancari R. , Calogero A. E. , Cianci A.
Published: March 2003

Summary: We describe the relation between clamping time and blood volume collected, and two enrichment systems of CD34+ stem cells from umbilical cord blood, in order to determine the criteria for an excellent recovery with high proliferative ability and bone marrow reconstitution.  After an obstetrician‐based cord blood collection, the purification of stem cells was performed either with a combination of monoclonal antibodies, negative selections, using the Stem Sep method, or with a positive cells selection owing to their surface CD34 antigens, using the Mini Macs system.  An excellent recovery of haematopoietic progenitors – burst forming unit erythroid; colony‐forming unit granulocyte and macrophage; and colony‐forming unit granulocyte, erythroid, monocyte, and macrophage – inversely related to an increase in clamping time, was achieved using the Mini Macs system (54 % of colonies with a 90 % purity), while the recovery of haematopoietic progenitors was 35 % (with a 80 % purity) using the Stem Sep method.  By clamping umbilical cord blood at an early stage, we obtained a greater number of CD34+ cells, and their clonogenic activity increased with enrichment. This is particularly useful considering that the number of CD34+ stem cells contained in a unit of placental blood is sufficient for transplanting into a child but not for an adult engraftment. Thus, using these methods, we obtain a larger number of CD34+ stem cells. This increases the possibility of reducing graft versus host disease in adult patients and produces survival rates similar to the ones we observed in transplantation of bone marrow from unrelated donors.
Genetic basis of color variation in leaf scars induced by the Kanzawa spider mite
Authors: Yano Shuichi , Kanaya Miki , Takafuji Akio
Published: March 2003

Abstract The color of scars induced on host leaves by the phytophagous spider mite Tetranychus kanzawai Kishida (Acari: Tetranychidae) can be categorized as red or white. We conducted a bi‐directional selection on the colors of leaf scars. In each of the selected strains, scars became uniformly red or white (‘Red’ and ‘White’ strains), indicating that scar color was genetically determined. Reciprocal and back‐crosses between strains suggested that the Red genotype was fully dominant over the White one and was controlled by a single locus. The performance index of adult females that induced red or white scars (‘Red’ and ‘White’ females) did not differ significantly among nine tested host plants. There seemed to be no advantages of heterozygosity at either the individual or the colony level. However, Red females defoliated host plants earlier than did White females. As a consequence, Red females dispersed from infested leaves earlier than White ones. The distribution pattern of Red and White females in the wild supported the hypothesis that genetic variation is maintained by different dispersal costs across environments.
Phloem amino acids and the host plant range of the polyphagous aphid, Aphis fabae
Authors: Wilkinson T. L. , Douglas A. E.
Published: March 2003

This study investigated the relationship between the essential amino acid requirement of the aphid Aphis fabae Scop. and the phloem sap amino acid composition of its host plants. The dietary amino acid requirement of A. fabae varied between clones. One or more of the eight clones of A. fabae tested displayed depressed larval survival, larval growth rate, or rm on diets lacking histidine, methionine, threonine, and valine, but none of the other five essential amino acids. The required amino acids corresponded closely to the essential amino acids that varied in relative concentrations among 16 plant species tested: histidine, threonine, tryptophan, and valine. It is suggested that the interclonal variation in the dietary requirements of an aphid species may contribute to the intraspecific variation in plant utilisation patterns. The phloem sap amino acid composition and sucrose : amino acid ratio did not differ consistently between host plant species of A. fabae and non‐host species, indicating that phloem amino acid composition is not an important factor in determining the host plant range of this aphid species.
Intradermal injection of Newcastle disease virus‐modified autologous melanoma cell lysate and interleukin‐2 for adjuvant treatment of melanoma patients with resectable stage III disease
Authors: Voit Christiane , Kron Martina , Schwürzer‐Voit Markus , Sterry Wolfram
Published: March 2003

Background: The value of active specific immunotherapy (ASI) for the treatment of solid tumours still has to be assessed. The objective was to test an autologous tumour cell vaccine for adjuvant treatment of stage III melanoma patients.

Patients and Methods: After open vaccination of 12 patients, another 17 patients were recruited for a randomized double‐blind trial comparing treatment with the vaccine (n = 9) and with a placebo (n = 8). Intracutaneous vaccinations were given postoperatively in weeks 2, 4, 6, 12, 24 and thereafter every 6 months if sufficient vaccine material was available. Patients were followed for 60 – 84 months.

Results: Median disease‐free survival time was 5 months for open‐treated, 4 months for verum‐treated and 6 months for placebo‐treated patients. Corresponding median overall survival times were 30.5, 18 and 18.5 months, respectively. There were no remarkable differences between the verum and the placebo group.

Conclusions: Adjuvant treatment of melanoma patients with an autologous ASI vaccine did not show clinical efficacy in this cohort of melanoma patients.
In situinvestigation of small fatigue crack growth in poly‐crystal and single‐crystal aluminium alloys
Authors: Zhang X. P. , Wang C. H. , Ye L. , Mai Y. ‐W.
Published: March 2003

Abstract In situscanning electron microscope observations of short crack growth in both a poly‐crystal and a single‐crystal alloy revealed that fatigue cracks may grow in a shear decohesion mode over a length that is several times the grain size, far beyond the conventional stage I regime. In the poly‐crystal aluminium alloy 2024‐T351, fatigue cracks were found to continue to grow along one shear band even after two mutually perpendicular shear bands had formed at the crack tip. For the single‐crystal alloy specimen with the loading axis being nearly perpendicular to its main shear plane, mode I fatigue cracks were found to grow along the shear band. These two types of fatigue crack growth pose a significant challenge to the existing fatigue crack growth correlating parameters that are based on crack‐tip opening displacement. In particular, it has been found that the cyclic crack‐tip opening displacement, which accounts for both large‐scale yielding and the lack of plasticity‐induced crack closure, is unable to unify the growth rates of short and long cracks in aluminium 2024‐T351, suggesting a possible dependence of crack growth threshold on crack length.
Closure of plane‐strain cracks under large‐scale yielding conditions
Authors: Wang C. H. , Rose L. R. F. , Newman J. C.
Published: March 2003

Abstract This paper presents computational and theoretical investigations of the plasticity‐induced crack‐closure of a plane‐strain crack under large‐scale yielding conditions. Solutions of the crack‐tip opening displacements for a stationary crack and a growing fatigue crack have been obtained using the finite element method. The self‐similar crack‐closure model has been extended to the plane strain case by introducing two plastic constraint factors: one for tension yielding and the other for compression yielding. These two plastic constraint factors are identified by matching the model predictions with the computational results. It is shown that the first constraint factor decreases rapidly with the applied stress while the second constraint factor is approximately equal to unity. The findings of this study allow the cohesive‐zone based crack‐closure model to be extended to plane‐strain cracks, especially under large‐scale yielding conditions.
Essential Roles for GPI-anchored Proteins in African Trypanosomes Revealed Using Mutants Deficient in GPI8
Authors: Lillico Simon , Field Mark C. , Blundell Pat , Coombs Graham H. , Mottram Jeremy C.
Published: March 2003

The survival of Trypanosoma brucei, the causative agent of Sleeping Sickness and Nagana, is facilitated by the expression of a dense surface coat of glycosylphosphatidylinositol (GPI)-anchored proteins in both its mammalian and tsetse fly hosts. We have characterized T. brucei GPI8, the gene encoding the catalytic subunit of the GPI:protein transamidase complex that adds preformed GPI anchors onto nascent polypeptides. Deletion ofGPI8 (to give Δgpi8) resulted in the absence of GPI-anchored proteins from the cell surface of procyclic form trypanosomes and accumulation of a pool of non–protein-linked GPI molecules, some of which are surface located. Procyclic Δgpi8, while viable in culture, were unable to establish infections in the tsetse midgut, confirming that GPI-anchored proteins are essential for insect-parasite interactions. Applying specific inducible GPI8 RNAi with bloodstream form parasites resulted in accumulation of unanchored variant surface glycoprotein and cell death with a defined multinuclear, multikinetoplast, and multiflagellar phenotype indicative of a block in cytokinesis. These data show that GPI-anchored proteins are essential for the viability of bloodstream form trypanosomes even in the absence of immune challenge and imply that GPI8 is important for proper cell cycle progression.
KDEL and KKXX Retrieval Signals Appended to the Same Reporter Protein Determine Different Trafficking between Endoplasmic Reticulum, Intermediate Compartment, and Golgi Complex
Authors: Stornaiuolo Mariano , Lotti Lavinia V. , Borgese Nica , Torrisi Maria-Rosaria , Mottola Giovanna , Martire Gianluca , Bonatti Stefano
Published: March 2003

Many endoplasmic reticulum (ER) proteins maintain their residence by dynamic retrieval from downstream compartments of the secretory pathway. In previous work we compared the retrieval process mediated by the two signals, KKMP and KDEL, by appending them to the same neutral reporter protein, CD8, and found that the two signals determine a different steady-state localization of the reporter. CD8-K (the KDEL-bearing form) was restricted mainly to the ER, whereas CD8-E19 (the KKMP-bearing form) was distributed also to the intermediate compartment and Golgi complex. To investigate whether this different steady-state distribution reflects a difference in exit rates from the ER and/or in retrieval, we have now followed the first steps of export of the two constructs from the ER and their trafficking between ER and Golgi complex. Contrary to expectation, we find that CD8-K is efficiently recruited into transport vesicles, whereas CD8-E19 is not. Thus, the more restricted ER localization of CD8-K must be explained by a more efficient retrieval to the ER. Moreover, because most of ER resident CD8-K is not O-glycosylated but almost all CD8-E19 is, the results suggest that CD8-K is retrieved from the intermediate compartment, before reaching the Golgi, whereO-glycosylation begins. These results illustrate how different retrieval signals determine different trafficking patterns and pose novel questions on the underlying molecular mechanisms.
Drs2p-related P-type ATPases Dnf1p and Dnf2p Are Required for Phospholipid Translocation across the Yeast Plasma Membrane and Serve a Role in Endocytosis
Authors: Pomorski Thomas , Lombardi Ruben , Riezman Howard , Devaux Philippe F. , van Meer Gerrit , Holthuis Joost C. M.
Published: March 2003

Plasma membranes in eukaryotic cells display asymmetric lipid distributions with aminophospholipids concentrated in the inner and sphingolipids in the outer leaflet. This asymmetry is maintained by ATP-driven lipid transporters whose identities are unknown. The yeast plasma membrane contains two P-type ATPases, Dnf1p and Dnf2p, with structural similarity to ATPase II, a candidate aminophospholipid translocase from bovine chromaffin granules. Loss of Dnf1p and Dnf2p virtually abolished ATP-dependent transport of NBD-labeled phosphatidylethanolamine, phosphatidylserine, and phosphatidylcholine from the outer to the inner plasma membrane leaflet, leaving transport of sphingolipid analogs unaffected. Labeling with trinitrobenzene sulfonic acid revealed that the amount of phosphatidylethanolamine exposed on the surface of Δdnf1Δdnf2 cells increased twofold relative to wild-type cells. Phosphatidylethanolamine exposure by Δdnf1Δdnf2 cells further increased upon removal of Drs2p, an ATPase II homolog in the yeast Golgi. These changes in lipid topology were accompanied by a cold-sensitive defect in the uptake of markers for bulk-phase and receptor-mediated endocytosis. Our findings demonstrate a requirement for Dnf1p and Dnf2p in lipid translocation across the yeast plasma membrane. Moreover, it appears that Dnf1p, Dnf2p and Drs2p each help regulate the transbilayer lipid arrangement in the plasma membrane, and that this regulation is critical for budding endocytic vesicles.