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We investigate the optical properties of nanostructures of antimony sulfide (Sb2S3), a direct-bandgapsemiconductor material that has recently sparked considerable interest as a thin film solar cell absorber.Fabrication from a nanoparticle ink solution and two- and three-dimensional nanostructuring with patternsizes down to 50 nm have recently been demonstrated. Insight into the yet unknown nanoscopic opticalproperties of these nanostructures is highly desired for their future applications in nanophotonics. Weimplement a spectrally broadband scattering-type near-field optical spectroscopy technique to study individualSb2S3nanodots with a 20-nm spatial resolution, covering the range from 700 to 900 nm. We show that inthis below-bandgap range, the Sb2S3nanostructures act as high-refractive-index, low-loss waveguideswith mode profiles close to those of idealized cylindrical waveguides, despite a considerable structuraldisorder. In combination with their high above-bandgap absorption, this makes them promising candidatesfor applications as dielectric metamaterials, specifically for ultrafast photoswitching. published

Das Schmerzmanagement nimmt einen besonderen Stellenwert in der klinischen Praxis ein, da inadaquat behandelte Schmerzen die Lebensqualitat der Patienten negativ beeinflussen und zu einem Anstieg der Krankheitskosten fuhren. Vor allem vulnerable Patientengruppen, wie zum Beispiel Patienten mit kognitiven Beeintrachtigungen, stellen den Prozess des Schmerzmanagements jedoch vor grose Herausforderungen. Nationale und internationale Studien zeigten im Hinblick auf die medikamentose Schmerztherapie der Patienten mit unter massive Versorgungsunterschiede zwischen Betroffenen mit kognitiver Beeintrachtigung und mental gesunden Patienten. Als mogliche Ursache hierfur wird in der Literatur die mangelnde Fahigkeit kognitiv Beeintrachtigter, ihre Schmerzen entsprechend zu ausern diskutiert. Weiterhin konnten Wissenslucken in Bezug auf ein adaquates Schmerzmanagement sowie Vorbehalte hinsichtlich der Wirkung und Dosierung der Analgetika bei Patienten mit kognitiven Einschrankungen seitens der am Behandlungsprozess beteiligten Professionen in den Studien identifiziert werden. Es fehlen evidenzbasierte Daten, die das aktuelle Management der Schmerztherapie bei kognitiv beeintrachtigten Patienten fur Deutschland beschreiben und Hinweise liefern, welche Prozesse konkret an die Bedurfnisse vulnerabler Patientengruppen adaptiert werden sollten.

Introduction: Studies suggest that in smokers attempting to quit smoking, the occurrence of stressful events is associated with smoking relapse. The purpose of this study was to deter- mine the effect of bupropion (an agent known to increase smoking cessation rates) on the craving, withdrawal, and mood response to stressful tasks administered in a laboratory setting. Methods: Response to three tasks (a speech, math, and cold pres- sor task) was measured in 65 smokers during ad libitum smoking. Smokers were then randomized to either bupropion or placebo. Fourteen days after starting medication, 43 subjects (28 receiving bupropion and 15 receiving placebo) quit smoking and laborato- ry procedures were repeated on the third day of abstinence. Results: Prior to cessation, stressors presented in a laboratory setting increased craving, nicotine withdrawal symptoms, and subjective distress but decreased positive affect. Thirty minutes of relaxation after the stressors did not result in these measures returning to prestress levels. During the nicotine withdrawal period, stress-induced responses were generally smaller than during the precessation period. Bupropion (relative to placebo) reduced overall levels of craving and withdrawal symptoms but did not have significant effects on response to stress during the nicotine withdrawal period. Conclusions: This study demonstrates that stress results in sustained increases in craving and withdrawal symptoms and changes in mood symptoms and that bupropion affects overall levels of these symptoms. Further research is needed to deter- mine if modifying response to stress is predictive of an effective treatment for facilitating smoking cessation.

Hydraulikzylinder steuern Bewegungsablaufe in einer Vielzahl von Geraten und Maschinen, die unter anderem auch im Freien in einem breiten Temperaturbereich eingesetzt werden. Unter Temperaturbedingungen von bis zu –20 °C war aufgrund bisheriger Werkstoffkonzepte bei Hydraulikzylindern Sprodbruchneigung mit der Gefahr von Personen- und Sachschaden durch ein mogliches mehrteiliges Versagen nicht sicher auszuschliesen. Forderungen der Zylinderbauer sowie Forderungen nach Leichtbaukonzepten haben die Entwicklung hochfester, zaher Zylinderrohrguten vorangetrieben. Das im Rahmen der F&E-Aktivitaten der Salzgitter Mannesmann Prazisrohr GmbH in Zusammenarbeit mit der Salzgitter Mannesmann Forschung GmbH (SZMF) entwickelte modifizierte Werkstoffkonzept lasst den Betrieb von Hydraulikzylindern im Temperaturbereich bis –20 °C sicher zu. Die erhohten Festigkeitslagen ermoglichen eine Wanddickenreduzierung der Zylinder von ca. 30 %. Ausgehend von warmgewalzten Rohren betragt die mogliche Wanddickenreduzierung bis zu 50 %.

Design: Selenium (Se) is required for the biosynthesis of selenocysteine-containing proteins. Several selenoenzymes, e.g. glutathione peroxidases and thioredoxin reductases, are expressed in the thyroid. Selenoenzymes of the deiodinase family regulate the levels of thyroid hormones. For clinical investigators, it is difficult to determine the role of Se in the etiology of (nodular-)goiter, because there are considerable variations of Se concentrations in different populations as reflected by dietary habits, bioavailability of Se compounds, and racial differences. Moreover, most previous clinical trials which investigated the influence of Se on thyroid volume harbored a bias due to the coexistence of severe iodine deficiency in the study populations. Methods: Therefore, we investigated the influence of Se on thyroid volume in an area with borderline iodine sufficiency. First, we investigated randomly selected probands for urinary iodine (UI) and creatinine excretion in spot urine samples and determined the prevalence of goiter and thyroid nodules by high-resolution ultrasonography. After this, we determined urinary Se excretion (USe) in probands with goiter as well as in matched probands without goiter. Adjustments between the two compared groups were made for age, gender, history of thyroid disorders, smoking, and UI excretion. Results: The mean USe and UI rates of all 172 probands were 24 μg Se/l or 27 μg Se/g creatinine and 96 μg I/l or 113 μg I/g creatinine indicating borderline selenium (20–200 μg/l) and iodine (100–200 μg/l) sufficiency of the study population. Probands with goiter (n=89) showed significantly higher USe levels than probands with normal thyroid volume (n=83; P < 0.05). USe rates were not influenced by present smoking or pregnancy. Conclusions: In our investigation, USe was not an independent risk factor for the development of goiter. The higher USe in probands with goiter in comparison with probands with normal thyroid volume is most likely a coincidence. Se does not significantly influence thyroid volume in borderline iodine sufficiency because the iodine status is most likely the more important determinant.

Objective: Thiocyanate (SCN−) has concentration dependent antithyroid properties and a role in the etiology of goiter has been suggested in several studies. In 1991 an epidemiological survey conducted in the region of Halle/Leipzig (Saxony), an area with significant air pollution, suggested an inverse relationship between urinary iodine (I−)/SCN− excretion and goiter prevalence. 10 years later, we reinvestigated the same industrial area to clarify if the situation has changed after the elimination of most industrial waste products and moreover, if SCN− excretion levels alone or in combination with air pollution or smoking as a SCN− source are critical for thyroid function. Design and methods: We investigated a cohort of 708 probands for I−, SCN− and creatinine excretion in spot urine samples and determined the prevalence of goiter and thyroid nodules by high resolution ultrasonography. Results: Probands with goiter (n = 79, 11%) had significantly higher urinary SCN− excretions than probands without (3.9 ± 2.8 vs 3.1 ± 3.4 mg SCN−/g creatinine) and significantly lower urinary I−/SCN− ratios than patients without thyroid disorders (41 ± 38 vs 61 ± 71 μg I−/mg SCN−/l). Mean urinary I− excretions were not different between probands with or without goiter. Smokers showed significantly elevated urinary SCN−/creatinine ratios in comparison to non-smokers (4.3 ± 4.3 vs 2.4 ± 2.1 mg SCN−/g creatinine). ANOVA revealed a prediction of thyroid volume through age (P < 0.001), gender (P < 0.001), body weight (P < 0.05) and smoking (P < 0.05). Conclusions: In our investigation, age, gender and smoking (raising SCN− levels by CN− inhalation) were predictive for thyroid volume and the urinary I−/SCN− ratios were able to detect probands with an increased risk of developing goiter in contrast to urinary I− excretion levels alone. These data suggest, that in an era and area of decreased cyanide pollution, SCN− may remain a cofactor in the multifactorial aetiology of goiter.

The purpose of this study was to assess the effect of bupropion on cytochrome P450 2D6 (CYP2D6) activity. Twenty-one subjects completed this repeated-measures study in which dextromethorphan (30-mg oral dose) was administered to smokers at baseline and after 17 days of treatment with either bupropion sustained-release (150 mg twice daily) or matching placebo. Subjects quit smoking 3 days before the second dextromethorphan administration. To assess CYP2D6 activity, urinary dextromethorphan/dextrorphan metabolic ratios were calculated after an 8-hour urine collection. Thirteen subjects received bupropion, and 8 received placebo. In those receiving active medication, the dextromethorphan/dextrorphan ratio increased significantly at the second assessment relative to the first (0.012 +/- 0.012 vs. 0.418 +/- 0.302; P < 0.0004). No such change was observed in those randomized to placebo (0.009 +/- 0.010 vs. 0.017 +/- 0.015; P = NS). At baseline, all subjects were phenotypically extensive CYP2D6 metabolizers (metabolic ratio

Systemisch applizierte Glukokortikoide zahlen in der Therapie der endokrinen Orbitopathie zur ersten Wahl. Ein intravenoser Einsatz von Glukokortikoiden in der klinischen Praxis war bisher in der Regel der Therapie einer schweren endokrinen Orbitopathie mit evtl. drohendem Visusverlust vorbehalten, obwohl es Hinweise auf eine geringere Rate an unerwunschten Nebenwirkungen im Vergleich zur oralen Applikation gibt. Fur den behandelnden Arzt stellt sich das Problem der Wahl der optimalen Applikationsform (oral oder intravenos), der Behandlungsdauer und der Dosierung der Glukokortikoide. Einschlusskriterien der Literaturrecherche waren: randomisierte, kontrollierte Studien zum Einsatz intravenoser und/oder oraler Applikation von Glukokortikoiden in der Therapie der endokrinen Orbitopathie mit oder ohne Begleittherapie. Diese Studien sollten die intravenose und orale Applikation moglichst direkt vergleichen und typische klinische Manifestationen einer endokrinen Orbitopathie entsprechend den Richtlinien der Amerikanischen Schilddrusengesellschaft und den gultigen Klassifikationssystemen sowie Nebenwirkungen der Steroidtherapie einschatzen. Der systemische Einsatz von Glukokortikoiden in der medikamentosen Therapie der endokrinen Orbitopathie ist die Therapie der Wahl (Evidenzklasse I a). In den analysierten Studien wurden initial bei der oralen Glukokortikoidtherapie zumeist Dosen von 60–100 mg (uber 7–14 Tage) in nachfolgend ausschleichender Dosierung uber mehrere Monate und bei der intravenosen Applikation Dosen von 500–1 000 mg Methylprednisolon in unterschiedlichen Intervallen verabreicht. Intravenos oder in Kombination intravenos/ oral applizierte Gesamtdosen an Glukokortikoiden variierten zwischen 1 und 21 g. Fur die intravenose Applikation sprach die signifikant haufigere Reduktion der klinischen Aktivitat der endokrinen Orbitopathie in zwei Studien. Die Recherche zeigt, dass Glukokortikoide in der Therapie der endokrinen Orbitopathie, in den beschriebenen Dosierungen, generell empfohlen werden konnen. Zuverlassige Vergleichsdaten fur beide Applikationsformen liegen hingegen noch nicht in ausreichender Qualitat und Quantitat vor, um eine endgultige Entscheidung zugunsten einer uberlegenen Applikationsform treffen zu konnen.

Objective To describe a kindred with a rare RET germline mutation in codon 791 and discuss potential management strategies. Methods We present clinical and biochemical data as well as results of mutation analysis in our study subjects and provide an overview of related published reports. Results Multiple endocrine neoplasia type 2 (MEN 2) is a familial cancer syndrome characterized by the development of medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia or adenoma. Germline mutations in RET are responsible for this autosomal dominant syndrome. Familial MTC is a variant of MEN 2A and can be caused by RET mutations in codon 791. Deaths from gene carriers with mutations in these codons have not yet been reported. In general, gene carriers with these RET mutations have late-onset MTC. Because only a few kindreds with this specific mutation have been identified and no long-term follow-up data are available, management of these patients can be a challenge. We illustrate the difficulties with decisions about not only when to perform thyroidectomy in these patients but also whether thyroidectomy should even be considered in such gene carriers with a benign course. Our reported kindred included four carriers with a codon 791 RET germline mutation, one of whom had the rare concomitant occurrence of acromegaly and MEN 2A. The 70- year-old mother had acromegaly and hyperparathyroidism but normal serum calcitonin levels and normal findings on thyroid ultrasound examination. She refused pentagastrin testing and any surgical intervention. The 37-year-old daughter had hypothyroidism, a small thyroid gland, and negative results of pentagastrin stimulation testing of calcitonin. The 18-year-old grandson also had a negative pentagastrin test result and normal thyroid ultrasound findings. The 5-year-old granddaughter had normal results of thyroid ultrasonography. In all patients, we recommended thyroidectomy. Conclusion Prospective studies are needed to clarify which patients with codon 791 RET germline mutation should undergo thyroidectomy. (Endocr Pract. 2004;10: 5-9)

After first implantation of a metallic stent into cardiac vessels in 1986 stent implantation has become a standard technique for treatment of coronary heart disease. During implantation of balloon-expandable stents, the structure of the stent undergoes high plastic deformation. Despite the fact, that stents are used for more than 15 years nearly no information about the mechanical and micro structural process during dilation are known. The present paper presents a detailed study and comparison of the experimental and the simulated expansion behaviour of metallic stents. Used material models are discussed and crystallographic details are presented. Dilation curves describe the behaviour of balloon-expandable coronary stents. The dilation behaviour depends on both the materials properties and the design of the stent. A numerical simulation of the dilation process by means of FE is suitable. A comparison of the experimental measurement and the numerical simulation demonstrates, that a Cauchy stress-strain material model should be used for numerical simulations. A local failure criterion is introduced, which considers void initiation as a criterion for mechanical failure. Moglichkeiten und Grenzen der Finite Element Simulation des Dilatationsverhaltens koronarer Stents Obwohl die Implantation von koronaren Stents klinisch 1986 zum erstenmal durchgefuhrt wurde, gehort sie heute bereits zu den Standardtherapien. Wahrend der Implantation werden ballonexpandierbare Stents von 1,8 mm Durchmesser auf uber 3,5 mm aufgeweitet und die Werkstoffe erfahren lokal hohe plastische Dehnungen. Trotz der 16 Jahre klinischer Praxis ist das Aufweitungsverhalten von Stents wissenschaftlich in Bezug auf die Mechanik und das Verhalten der Werkstoffe wenig untersucht. In dieser Arbeit werden daher messtechnisch ermittelte Ergebnisse denen aus Finite Element Simulationen gegenubergestellt und bewertet. Dabei werden die verwendeten Werkstoffmodelle vorgestellt und diskutiert. Dieser Vergleich zeigt, dass realitatsnahe Simulationsrechnungen nur auf der Grundlage von wahren-Spannung-Dehnung Kurven moglich sind. Daruber hinaus kann man so ein lokales Schadigungskriterium einfuhren, dass lokale Porenbildung als Beginn der Schadigung berucksichtigt.

Shaping the temporal response of photoreceptors is facilitated by a well-balanced second messenger cascade, in which two neuronal Ca(2+)-sensor proteins operate in a sequential relay mechanism. Although they share structurally similar sensing units, they differentially activate the same target protein. Here, as a prototypical case in Ca(2+)-mediated signal processing, we investigate differential cellular responsiveness in protein conformational dynamics on a nanosecond time scale. For this, we have site-specifically labeled cysteine residues in guanylate cyclase-activating protein GCAP1 by the fluorescent dye Alexa647 and probed its local environment via time-resolved fluorescence spectroscopy. Fluorescence lifetime and rotational anisotropy measurements reveal a distinct structural movement of the polypeptide chain around position 106 upon release of Ca(2+). This is supported by analyzing the diffusional dye motion in a wobbling-in-a-cone model and by molecular dynamics simulations. We conclude that GCAP1 and its cellular cognate GCAP2 operate by distinctly different switching mechanisms despite their high structural homology.

Due to the fact that the risk of Ni-allergies are more and more important for modern therapies, the need of Ni-free implant materials becomes increasingly vital. Beside Co- and Ti-base alloys the new Ni-free high-Nitrogen steels might offer an attractive alternative to these expensive materials. The high-Nitrogen and Ni-free stainless steel X13CrMnMoN18-4-3 (1.4452) is investigated in the solution annealed state as to its corrosion, fatigue and sliding wear behaviour in Ringer solution. Under all test stresses this steel revealed a better behaviour as the conventional 316L-type X2CrNiMo18-15-3. When compared to literature data of solution annealed Ni-containing high-Nitrogen steels and Ni-free Co-base alloys the 1.4452 shows similar bahaviour. The good fatigue behaviour is attributed to the low stacking fault energy resulting in the total absence of climbing and cross slip. The corrosion properties can be related to the amount of dissolved N. The sliding wear behaviour in a self-mating contact benefits from both the low stacking fault energy and the characteristic corrosion mechanisms. Together with the elsewhere reported non-cytotoxicity the steel X13CrMnMoN18-4-3 (1.4452) can be considered being suitable for medical applications. Mechanische, chemische und tribologische Eigenschaften des Ni-freien, hoch stickstoffhaltigen Stahls X13CrMnMoN18-14-3 (1.4452) Aufgrund der Probleme mit moglichen Ni-Allergien besteht in der Medizintechnik die Forderung nach Ni-freien Werkstoffen. Neben den bekannten Co- und Ti-Basis Legierungen bieten die Ni-freien hochstickstoffhaltigen Stahle eine kostengunstige Alternative. Der Stahl X13CrMnMoN18-14-3 (1.4452) ist ein Vertreter aus dieser Gruppe und wird in diesem Beitrag im losungsgegluhten Zustand auf seine Korrosions-, Ermudungs- und Verschleiseigenschaften in Ringer Losung untersucht und diskutiert. Im Vergleich zum ublichen medizinischen Edelstahl X2CrNiMo18-15-3 zeigt der 1.4452 unter allen Beanspruchungen bessere Eigenschaften. Das gunstigere Ermudungsverhalten wird durch die niedrige Stapelfehlerenergie bestimmt, wahrend die besseren Korrosionseigenschaften auf den gelosten N zuruckzufuhren sind. Das sehr gute Gleitverschleisverhalten im artgleichen Kontakt wird durch das Zusammenwirken von beiden erreicht. Berucksichtigt man weiterhin das nicht-zytotoxische Verhalten, kann man den Stahl 1.4452 als tauglich fur medizinische Anwendungen bezeichnen.

The present work presents a new austenitic high-nitrogen and nickel-free steel X13CrMnMoN18-14-3, (1.4452). The cyclic fatigue behaviour of this materials was investigated under simulated body conditions. When compared to solution annealed CrNiMo-steels, fatigue endurance limit is higher. The pitting potential in Ringer's solution was measured being 1.1 V, which is in the range of CoCr29Mo6. Hence, the austenitic high-nitrogen steel X13CrMnMoN18-14-3 may be a promising alternative to CrNi-Mo-steels due to the absence of nickel and improved mechanical and chemical properties.

Since the introduction in 1986 today hundreds of thousands of stent implantations are carried out worldwide. Nevertheless, only few examinations of the mechanical behavior of coronary stents have been carried out. It becomes obvious, that the burst open pressure and the recoil of a stent expansion curve depend on the design and the pre-deformation of the stent. Additionally the recoil depends also on the maximum dilation pressure. The environmental electrolyte does not influence the mechanical behavior. Despite the high amount of plastic deformation during the expansion process, no strain hardening can be observed. During dilation some metallic ions are released into the solution. After the plastic deformation a repassivation of the material occurs. Over a period of three months after the dilation, no metallic ions can be detected in the solution without further mechanical deformation.

HISTORY AND ADMISSION FINDINGS A 78-year-old woman presented with a first episode of syncope. She reported increasing fatigue and dyspnoea upon exertion over a period of 20 years and chest pain 2 months prior to admission. Auscultation revealed fixed doubling of the second heart sound. INVESTIGATIONS Laboratory tests showed increased troponin I. Transaminases were moderately elevated. Chest X-ray showed an enlarged right heart and a dilated pulmonary artery (2 cm). Echocardiography discovered a large secundum atrial septal defect with a diameter of 3 cm but no right to left shunt (no Eisenmenger reaction). Cardiac catheterization revealed a stenosis of the right coronary artery and severe systolic pulmonary hypertension of 80 mmHg. DIAGNOSIS, TREATMENT AND COURSE A significant stenosis of the right coronary artery was successfully dilated. The ASD was closed by interventional implantation of a commercial closure device (Amplatzer). One month later, echocardiography indicated in an estimated systolic pulmonary pressure of 30 mmHg. The patient's condition improved considerably. CONCLUSION This case is remarkable in that a very large ASD was asymptomatic up into old age and without the development of an Eisenmenger reaction. Also, large ASD can be by catheterization with the appropriate closure device. Fixed pulmonary hypertension is not obligatory. Non-invasive closure is a good alternative of surgery in elderly patients with risk factors.

We present and investigate a novel approach towards broad-bandwidth near-field scanning optical spectroscopy based on an in-line interferometer for homodyne mixing of the near field and a reference field. In scattering-type scanning near-field optical spectroscopy, the near-field signal is usually obscured by a large amount of unwanted background scattering from the probe shaft and the sample. Here we increase the light reflected from the sample by a semi-transparent gold layer and use it as a broad-bandwidth, phase-stable reference field to amplify the near-field signal in the visible and near-infrared spectral range. We experimentally demonstrate that this efficiently suppresses the unwanted background signal in monochromatic near-field measurements. For rapid acquisition of complete broad-bandwidth spectra we employ a monochromator and a fast line camera. Using this fast acquisition of spectra and the in-line interferometer we demonstrate the measurement of pure near-field spectra. The experimental observations are quantitatively explained by analytical expressions for the measured optical signals, based on Fourier decomposition of background and near field. The theoretical model and in-line interferometer together form an important step towards broad-bandwidth near-field scanning optical spectroscopy.

Pain is a significant problem in clinical practice and its control is one of the most important challenging aspects as pain has a major impact on patients' quality of life and health care costs. Particularly vulnerable persons, like cognitively impaired patients are challenging for pain management and underline its increasing relevance.National and international studies showed significant differences concerning pain therapy between cognitively impaired and cognitively intact patients. A possible cause of this may be that patients who are cognitively impaired are only in a restricted way able to express their pain. Furthermore, knowledge gaps and reservations concerning the effect and dosage of analgesics among cognitively impaired patients could be identified on the involved professions.Further investigations in Germany are needed as deficient treatment remains a persistent problem and evidence-based data are missing. These investigations should describe the status quo of pain management for cognitively impaired patients and provide information which processes have to be adapted to the needs of these vulnerable patients.

Metal ions released from implanted stents into the surrounding tissue may contribute to vascular reactions which cause restenosis in about 30%. This assumption prompted us to investigate short term effects of metal ions (Ag, Al, Cr, Fe, Mo, Ni, V, all applied as chloride salts) on proliferation of swine aortic smooth muscle cells (SMC) and a myoblastic cell line (C2C12). Cell confluence was 30 or 50% when metal ions were added and cell growth was monitored with the MTT-test after 2 days. A clear concentration dependence of acute toxicity of the different metal ions was found for both cell types. The order of toxicity indicated by IC50 values was V > Ni > Fe > Mo > Al > Cr. The nearly insoluble silverchloride exerted unclear effects. In experiments starting at high confluence, the apparent toxicity of Fe, Ni, and V was reduced. Al, which to our knowledge is not a major constituent in medical stents, was the only metal ion found here to cause a slightly increased proliferation, but this effect was restricted to the low concentration range (16–250 μmol/l). In general, results for both cell types, C2C12 and SMC, were very similar. We conclude that short term effects of metal ions, which may be released in the interface of stent and vessel wall tissue, comprise a reduction rather than a stimulation of cell proliferation. However, restenosis may be initiated as a complex tissue reaction to primary toxic metal effects. Wirkungen von Metallionen auf die Proliferation von glatten Muskelzellen der Aorta und myoblastischen Zellenin vitro Metallionen, die aus Stent-Materialien freigesetzt werden, tragen moglicherweise zu Reaktionen der Gefaswand bei, die in etwa 30% der Falle zu einer Restenose fuhren. Um diese Annahme zu prufen haben wir die kurzzeitige Wirkung von Metallionen (Ag, Al, Cr, Fe, Mo, Ni, V, eingesetzt als Chloride) auf die Proliferation von glatten Muskelzellen (SMC) aus der Schweine-Aorta sowie von myoblastischen Zellen der Maus (C1C12-Zellen) untersucht. Die Konfluenz der Zellen betrug zum Zeitpunkt der Metallionen-Zugabe zum Kulturmedium 30 oder 50%; das Wachstum der Zellen wurde nach 2 Tagen mit dem MTT-Test kontrolliert. Bei beiden Zelltypen wurde fur fast alle Metalle eine akute, konzentrationsabhangige Hemmung des Wachstums gefunden. Der Vergleich der Toxizitaten anhand der entsprechenden IC50 Werte ergab V > Ni > Fe > Mo > Al > Cr. Das kaum losliche Silberchlorid bewirkte unklare Effekte. In Experimenten, bei denen zu Beginn hohe Konfluenz gewahlt worden war, war der toxische Effekt von Fe, Ni und V vermindert. Al, das nicht zu den Hauptbestandteilen derzeit klinisch verwendeter Stents gehort, loste in geringen Konzentrationen (16–250 μmol/l) eine leichte Steigerung der Proliferation aus. Der Vergleich von C2C12 Zellen und SMC ergab eine weitgehende Ubereinstimmung der Testergebnisse. Wir schliesen aus den Befunden, dass Metallionen, sofern sie ins Interface rund um Stents gelangen, zunachst eher eine Verminderung als eine Steigerung der Zellproliferation bewirken. Eine Restenose, die eine komplexe Gewebereaktion darstellt, konnte jedoch eine verzogerte Folge toxischer Einwirkung von Metallionen sein.

OBJECTIVE—To determine whether corrodible materials may be safely used as biodegradable cardiovascular implants. DESIGN—Corrodible iron stents (> 99.8% iron) were produced from pure iron and laser cut with a stent design similar to a commercially available permanent stent (PUVA-AS16). A total of 16 NOR-I stents were implanted into the native descending aorta of 16 New Zealand white rabbits (mean luminal diameter at the implantation site 3.4 mm, balloon diameter to vessel diameter ratio 1.13). RESULTS—No thromboembolic complications and no adverse events occurred during the follow up of 6-18 months. All stents were patent at repeat angiography after 6 (n = 9), 12 (n = 5), and 18 months (n = 2) with no significant neointimal proliferation, no pronounced inflammatory response, and no systemic toxicity. CONCLUSIONS—This initial in vivo experience suggests that degradable iron stents can be safely implanted without significant obstruction of the stented vessel caused by inflammation, neointimal proliferation, or thrombotic events. Keywords: congenital heart disease; corrosion; stents; biodegradation

Rationale: Studies with laboratory animals and humans suggest that dopamine may play a role in maintaining cigarette smoking behavior via its interactions with nicotine. Objectives: This study was designed to replicate and extend previous findings showing that the dopamine D2 antagonist, haloperidol, produces blockade of smoking reward and compensatory increases in smoking. Methods: We studied 20 subjects in a 2×3 within-subjects design, with nicotine-containing or denicotinized cigarettes crossed with oral placebo, haloperidol 1 mg, or haloperidol 2 mg. Subjects attended six sessions during which they received one of the cigarette/drug combinations, and smoked under both controlled and ad libitum conditions. Cigarette and mood ratings and smoking behavior were assessed. Results: Haloperidol reduced the number of cigarettes smoked and the carbon monoxide boost associated with both types of cigarettes, at doses that did not appear to produce clinically significant behavioral effects. Conclusions: Dopamine appears to play a role in mediating smoking behavior, but this may occur through a non-nicotine mechanism.

Die Einfuhrung von koronaren Stents stellt einen Meilenstein in der interventionellen Kardiologie dar. Die Uberlegenheit dieses Behandlungsprinzips gegenuber der alleinigen Ballonangioplastie konnte in randomisierten klinischen Untersuchungen belegt werden und hat zu einer deutlichen Zunahme der Stentimplantationen seit ihrer Einfuhrung im Jahr 1986 gefuhrt. Obwohl durch die Stentimplantation die Behandlung der koronaren Herzerkrankung deutlich verbessert wurde, bleibt die Restenose ein bisher ungelostes Problem. Neben interventionstechnischen und krankheitsimmanenten Einflussgrosen scheint dem Stent als Implantat eine entscheidende Rolle im Restenoseprozess zuzukommen. Mit der Einfuhrung der Stentimplantation in die kardiologische Routine ist auch die Anzahl kommerziell verfugbarer Stents gestiegen, die sich sowohl im Werkstoff als auch im Design unterscheiden. Obwohl erste Untersuchungen mit abbaubaren Polymeren und Metallen vielversprechende Ergebnisse gezeigt haben, werden heute verfugbare Stents fast ausnahmslos aus metallischen Werkstoffen gefertigt. Wahrend Edelstahl bei der Herstellung der ersten Stentmodelle fast ausschlieslich Verwendung fand, und dem verwendeten Material nur untergeordnete Bedeutung zukam, zeigen neuere Untersuchungen, dass der verwendete metallische Werkstoff Auswirkungen auf das Ausmas der Restenose hat. So unterscheiden sich Metalllegierungen nicht nur in ihren mechanischen Eigenschaften sondern auch in ihrer Biokompatibilitat, zwei Faktoren, die entscheidend bei der Induktion von Entzundungsprozessen und Gewebeproliferation mitwirken. In der vorliegenden Arbeit werden in einem ersten Teil die verschiedenen heute verwendeten oder in der Erprobung befindlichen metallischen Materialen im Hinblick auf ihre werkstofftechnischen Eigenschaften vorgestellt. Des Weiteren werden Ergebnisse aus tierexperimentellen und klinischen Untersuchungen dargestellt, die sich mit der Biokompatibilitat dieser metallischen Werkstoffe sowie deren Auswirkung auf die Restenose nach endovaskularer Implantation befassen.

The immuno-inflammatory response to titanium plates used for the internal fixation of long bones was studied histologically. The soft tissue adjacent to the surface of titanium plates was examined by means of immunohistochemical methods in ten patients. The tissue was discoloured black as a sign of metallosis in 7 patients. Titanium particles located in macrophages ( CD68 +) were observed in all patients. Some of them expressed MHC class II molecules. T-lymphocytes (CD45RO +) were detected in the vicinity of titanium particles. CD8 positive cells were also observed, whereas B-lymphocytes (CD79a +) were absent. The presence of titanium was confirmed by energy-dispersive X-ray analysis.

This paper proposes a new method for biomedical electromagnetic inverse problems based on the technique of maximum mutual information. The new method is different from the conventional methods for it will not depend on the widely used regularization technique. The new method provides a general paradigm for developing algorithms dealing with various biomedical inverse problems that can be described using lead field, including localization and imaging of neural source activities in brain and heart from EEG/MEG and ECG/MCG; it is also possible to apply it to other, electromagnetic inverse problems like electrical impedance tomography. This paper mainly provides the theoretical development, with MEG inverse problems as case studies.

Experiments are carried out to examine the dilatation properties of metallic stents. Therefore a test rig has been developed. Also the dilatation behaviour of stents out of different materials are investigated. Additionally numerical simulations of dilatation are carried out. Because balloon expandable stent systems exist of the stent and a balloon catheter, the balloon catheter is examined before the investigation of the stent systems. The results show a reproducible and similar dilatation behaviour for all stents. Titanium as a material with an advanced biocompatibility shows advantages in the dilatation behaviour against the stainless steel stents. A qualitative equality between simulation and measurement of the dilatation behaviour can be noticed. The results indicate the possibility to numerically simulate and to optimise the dilatation behaviour by a combination of simulation and measurement. The preclinical measurement can be reduced to some prototypes. Messung und rechnergestutzte Simulation des Verhaltens marktgangiger koronarer Stentsysteme Es werden Untersuchungen zum Verstandnis des mechanischen Dilatationsverhaltens an einer eigens dafur entwickelten Prufeinrichtung auserhalb eines Gefases durchgefuhrt und diskutiert. Weiterhin befast sich die vorliegende Arbeit mit dem Verhalten der unterschiedlichen Materialien bei Dilatation. Diese Arbeiten werden begleitet von entsprechenden Finite-Element-Berechnungen sowie licht- und rasterelektronenmikroskopischen Untersuchungen. Da Stentsysteme aus einem Ballonkatheter und einem darauf befestigten Stent bestehen, werden vor der Untersuchung der Stentsysteme die Ballonkatheter einzeln untersucht. Bei der Dilatation der verschiedenen Stents kann eine einheitliche Form der Dilatationskurve festgestellt werden. Dabei zeigt z. B. Titan als bevorzugtes biokompatibles Material Vorteile gegenuber Stahl im Aufweitungsverhalten. Eine Simulation des Dilatationverhaltens last eine qualitative Ubereinstimmung zwischen der Messung und Simulation erkennen. Durch die Kombination von Simulation und Messung ergibt sich also die Moglichkeit das Verhalten neuer Stents numerisch zu simulieren und zu optimieren. Die vorklinische Messung kann sich dabei auf wenige Prototypen beschranken.

In Lorentz force evaluation the model of the permanent magnet influences the accuracy of the forward solution. We assess the forward solution by modelling the permanent magnet with a varying number of magnetic dipoles. Our model comparison shows that a model with 10 dipoles is well suited for the forward calculation of Lorentz forces.

de WIT, H., M. CLARK AND L. H. BRAUER. Effects of d-amphetamine in grouped versus isolated humans. PHARMACOL BIOCHEM BEHAV 57(1/2) 333––340, 1997.—This study was designed to determine whether the subjective, behavioral or physiological effects of a stimulant drug in humans depend on whether subjects are tested under isolated or social conditions. Forty-two subjects were randomly assigned to either the Social (SOC) or Isolated (ISO) condition. SOC subjects participated in 4 h laboratory sessions in groups of 3 or 4, whereas ISO subjects participated in the sessions alone. All subjects participated in three sessions, during which they received capsules containing d-amphetamine (10 or 20 mg) or placebo, in mixed order under double blind conditions. Subjective, physiological and behavioral measures were obtained at regular intervals. d-amphetamine produced dose-related, prototypic stimulant effects on many measures, including self-reported mood states, behavioral indices and physiological measures. Most of these effects were unaffected by the setting in which subjects were tested (SOC vs ISO). However, body temperature was overall higher in the SOC group, and there was a trend for d-amphet-amine to produce greater hyperthermic effects in the SOC group. In addition, 10 mg d-amphetamine increased heart rate in the SOC group but not in the ISO group. The results suggest that, like in laboratory animals, some of the effects of stimulants in humans are greater under aggregated conditions. However, unlike in the animal studies, this observed enhancement of the drug's effects under aggregated conditions was limited to physiological measures and did not apply to other subjective or behavioral measures.

We investigate the radiation patterns of sharp conical gold tapers, which were designed as adiabatic nanofocusing probes for scanning near-field optical microscopy (SNOM). Field calculations show that only the lowest order eigenmode of such a taper can reach the very apex and thus induce the generation of strongly enhanced near-field signals. Higher-order modes are coupled into the far field at finite distances from the apex. Here, we demonstrate experimentally how to distinguish and separate between the lowest and higher-order eigenmodes of such a metallic taper by filtering in the spatial frequency domain. Our approach has the potential to considerably improve the signal-to-background ratio in spectroscopic experiments at the nanoscale.

1. The cardiorespiratory and renal responses to 3 h of normobaric whole-body hypoxic hypoxia (FiO2 = 0.12) as well as to arterial chemoreceptor stimulation by the oral administration of 100 mg almitrine bismesylate during normoxia were measured in 12 normotensive young men undergoing water diuresis. A third series of responses obtained under comparable conditions in the same subjects served as time controls. 2. No significant changes could be detected over time in the parameters measured in control experiments. The subjects reacted to both whole-body hypoxic hypoxia and to pharmacological chemoreceptor stimulation with significant increases in heart rate, tidal volume, minute ventilation and filtration-fraction. Overall renal vascular resistance rose significantly in hypoxia; increases in renal vascular resistance in almitrine experiments were not significant. 3. Renal fractional lithium excretion decreased significantly in response to whole-body hypoxic hypoxia and increased slightly in response to almitrine. Fractional urine and sodium excretion showed negligible changes. 4. The data indicate that, in humans, both almitrine and whole-body hypoxic hypoxia affect not only alveolar ventilation but also renal haemodynamics. 5. The renal electrolyte excretion pattern suggests that under certain circumstances (e.g. dilated renal vascular bed) acute, but well-tolerated, whole-body hypoxic hypoxia can simultaneously stimulate renal proximal tubular sodium reabsorption and inhibit distal tubular sodium reabsorption. The renal tubular responses also indicate that almitrine may influence renal tubular lithium reabsorption by, thus far, unknown mechanisms.

Recent clinical reports indicate that combined administration of phentermine and fenfluramine may have useful effects in the treatment of drug abuse. The present study was designed to evaluate the subjective and mood-altering effects of these drugs, alone and in combination, in normal healthy volunteers. Seven male and five female volunteers participated in an eight-session, double-blind study in which each subject received each of the following drug conditions: d-amphetamine (10 and 20 mg), phentermine (30 mg), fenfluramine (40 and 80 mg), phentermine (30 mg) with fenfluramine (40 mg), phentermine (30 mg) with fenfluramine (80 mg), and placebo. Sessions were conducted in a laboratory setting two or three days a week. Subjects completed standardized self-report questionnaires and psychomotor tests before and at regular intervals after each drug administration. Phentermine produced effects that were similar to those of d-amphetamine, whereas fenfluramine produced different and apparently aversive effects (e.g., it increased measures of anxiety and confusion). Phentermine reduced the apparently aversive effects of fenfluramine when the two drugs were given together. These results suggest that the combination of phentermine and fenfluramine would have a low potential for abuse.

This is a descriptive report on the relationship between the pharmacokinetics and pharmacodynamics of d-amphetamine in healthy, normal volunteers. Six men, aged 22 to 31, attended two experimental sessions during which they received single oral doses of 20 mg of d-amphetamine. Plasma levels of drug and measures of drug effect were collected predrug and at regular intervals for 24 hours after drug administration. Plasma drug levels peaked at 4 hours and remained at detectable levels for 24 hours after drug administration. Subjective ratings, including "feel drug" and "feel high" peaked at 1 1/2 to 2 hours and returned to baseline levels by 3 to 4 hours. Evaluation of phase plots (i.e., drug effect vs. drug concentration) indicated that acute tolerance developed to the subjective but not to the cardiopressor effects of d-amphetamine. This finding implies that individuals who repeatedly administer the drug to maintain certain levels of subjective effects may increase plasma drug levels and physiologic effects to toxic levels.

The role of dopamine in d-amphetamine-induced euphoria has not been systematically examined in normal volunteers. Therefore, we examined the effects of the dopamine antagonist, pimozide, on responses to d-amphetamine in healthy volunteers, using a within-subjects, double-blind design. Ten subjects received single oral doses of d-amphetamine (0, 10, 20 mg) 2 hours following pretreatment with pimozide (0, 1, 2 mg). Subjective, behavioral, and physiological effects were assessed predrug and for 3 hours after d-amphetamine administration. d-Amphetamine alone produced prototypic effects on a variety of measures, including euphoria and drug liking. Pimozide did not produce any effects when administered alone and produced inconsistent effects on responses to d-amphetamine. Although higher doses of pimozide may be needed to antagonize the euphorigenic effects of d-amphetamine, these results raise the possibility that the role of dopamine in the subjective effects of stimulants may be more complex than initially appreciated.

The purpose of this study was to compare the subjective effects of the selective serotonin reuptake inhibitor, paroxetine, to those of the prototypic stimulant, d-amphetamine. Ten healthy volunteers attended 5 sessions and received paroxetine (10, 20, 50 mg), d-amphetamine (20 mg), and placebo. Subjective effects were measured at regular intervals for 26-30 h. Paroxetine and d-amphetamine produced highly dissimilar effects on mood. For example, whereas d-amphetamine increased ratings of euphoria, drug high, and desire for drug, paroxetine produced no effects on these measures. Conversely, whereas paroxetine increased ratings of Confusion and Fatigue, d-amphetamine did not. These findings suggest that serotonin does not play a significant role in mediating the positive subjective effects of stimulant drugs.

In a comprehensive study batch and continuous production of citric acid has been investigated. Fermentations in the reciprocation-jet-bioreactor (RJBR) have been carried out with the fungi Aspergillus niger. In the present paper only the results of continuous fermentations are presented. The paper discusses the influence of medium composition in the influent, input of biomass and frequency of reciprocating motion on citric acid production.

We describe a patient who underwent thoracic radiation therapy for biopsy-proven pulmonary spindle cell sarcoma in the left lower lobe, 15 months after birth. At the age of 37 she developed shoulder pain, fatigue, and progressive exertion dyspnoea. Chest X-ray revealed a pulmonary mass in the left lower lobe due to a cytology-proven malignant tumour.The patient underwent left pneumonectomy. Histology revealed a myosarcoma of the lung, similar to the previous sarcoma. Furthermore, the patient was diagnosed to have Turner syndrome mosaic and chromosomal analysis revealed a translocation t(1;13) in 3/50 metaphases. However a germline mutation of the p53 tumour suppressor gene was excluded. After 2 years of follow-up the patient is stable and there are no signs of recurrence of the tumour.We conclude a re-occurrence of this very rare malignant disorder of the lung after a 36-year interval in a patient with Turner syndrome mosaic. Following initial curative radiation therapy, with a remission over 36 years, lung resection was now successfully performed.