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Treatment recommendations for cytoreductive treatment of patients with polycythemia vera (PV) are well established. However, the clinical use and limitation of phlebotomies remain a matter of current debate (Barbui et al, Leukemia, 32; Heidel et al, Leukemia, 32). While multicenter trials investigating therapeutic strategies for PV have been conducted at specialized academic centers, the majority of patients is treated in an outpatient (ambulatory) setting. The aim of this study is to evaluate the 'real live' situation especially in regard to the use of phlebotomy and cytoreductive therapy in a cohort of 1500 patients from a survey conducted at private practices and primary care centers. Eligible centers treating patients with MPN in Germany were recruited to participate in a paper-pencil based ongoing survey conducted from December 2018 and planned until December 2019. Hematologists were asked to report from patient charts. Descriptive analyses were conducted to assess for therapeutic interventions and outcomes and examined by reported prognostic risk scores, symptom scores, and clinical response criteria. For this interim analysis (data cutoff on May 31, 2019) a total of 11 centers participated in a retrospective survey and provided data on 434 patients. Gender was balanced with 211 (48.6%) male and 223 (51.4%) female patients. Most patients were of older age (mean 71.4 years; 62.7 years at diagnosis and 63,4% over the age of 60), which is a main risk factor according to published criteria (Tefferi et al, Am J Hematol, 94). 154 patients (35.5%) had a disease history of more than 10 years, 95 pts (21.9%) 6 to 10 years and 42.6% less than 6 years. Thromboembolic complications were reported in 100 patients (23.0%) at time of diagnosis and for 61 (14.1%) during treatment. Additional cardiovascular (CV) risk-factors were reported for 320 patients (73.7%), whereas 107 (24.7%) had none (and no data available in 1,6% (n=7) of cases). Hypertension was the most prevalent CV risk factor with 86.9% (n=278) affected, followed by hypercholesteremia 18.8% (n=60), diabetes mellitus 16.2% (n=52) and smoking 15.9% (n=51). Phlebotomy was the primary therapy in 301 patients (69.4%). Of those, 83 (27.6%) received 1-3 phlebotomies/year, 113 (37.5%) 4-6/year, 71 (23.6%) 7-12 times/year and 8 pts (2,6%) >13 times/year. Main triggers to start pharmacologic cytoreduction included the presence of high-risk criteria (53.2%) and insufficient disease control (22.6%). Of note, asymptomatic iron deficiency (5.6%), symptomatic iron deficiency (9.3%) and intolerance to phlebotomy (5.3%) have been reported in a significant number of patients and contributed to the limitation of phlebotomy treatment. Choice of cytoreductive agents included hydroxycarbamide (n=320; 73.3%), JAK-inhibitors (n=80, 18.4%), Interferon alpha (n=15; 3,5%), IMIDEs (n=2; 0.5%) and other cytoreductive agents (n=6; 1.4%). While 11 patients (2.5%) required combination of cytoreductive agents, 137 (31.3%) patients had a persistent need for phlebotomy. In summary, the patient population investigated here was older than in published large multicenter trials. Age was the main factor accounting for the majority of patients being categorized as 'high risk'. Although the majority of patients (>60%) presented as 'high risk' according to international guidelines, 69.4% of patients received phlebotomy as primary therapeutic approach, in part at high frequency (>25% with more than 7 phlebotomies per year). The low number of primary cytoreductive treatment and occurrence of symptomatic iron deficiency in 9.3% and of intolerance in 5.3% of patients indicates the need to reconsider indication and limitations of phlebotomy. We conclude that phlebotomy as a prophylactic measure of risk reduction should result in mild iron-deficient erythropoiesis and hematocrit control without inducing a severe iron-deficiency syndrome as indicated by increased levels of soluble transferrin-receptor or Zn-protoporphyrin. Pharmacologic cytoreduction is necessary for high risk patients older than 60 years or with previous thromboembolic complications. For patients, who require permanent phlebotomies at high frequency for sufficient hematocrit control ( Disclosures Wunschel: Novartis Inc.: Employment. Hochhaus:MSD: Research Funding; Incyte: Research Funding; BMS: Research Funding; Pfizer: Research Funding; Novartis: Research Funding. Heidel:Novartis: Research Funding.

Growing literature indicates that emotional reactivity and regulation are strongly linked to genetic modulation of serotonergic neurotransmission. However, until now, most studies have focused on the relationship between genotypic markers, in particular the serotonin transporter-linked polymorphic region (5-HTTLPR), and neural structures using MRI. The current study aimed to bridge the gap between the relevant MRI literature on the effects of the 5-HTTLPR genotype and the research tradition focusing on transient lateralized changes of electrocortical activity in the prefrontal cortex using electroencephalography (EEG). Lateral shifts of EEG alpha asymmetry in response to an aversive film consisting of scenes of real injury and death were assessed in healthy participants (n = 165). To evaluate the specificity of the 5-HTTLPR effect, participants were also tested for the COMT Val158Met polymorphism which is linked to dopamine inactivation. While viewing the film, individuals homozygous for the 5-HTTLPR short allele displayed a clear lateral shift of dorsolateral frontal activity to the right, which was virtually absent in participants carrying the long allele. The heightened electrocortical response to the aversive stimulation and its direction indicates a greater propensity of s/s homozygotes to experience withdrawal oriented affect in response to negative emotion cues in the environment. Moreover, together with previous research the findings support the notion of a link between the serotonergic system and self-regulation related to avoidance motivation, and a link between the dopaminergic system and self-regulation related to approach motivation.

The aim of the present study was to examine whether interindividual differences in the coupling or decoupling of prefrontal and posterior cortices during the exposure to social-emotional information may predict an individual's positive emotional responsiveness. Susceptibility to humor was assessed in a behavioral paradigm several weeks after the EEG recordings. State-dependent changes of prefrontal-posterior EEG beta coherence were recorded during stimulation with other people's auditory expressions of cheerfulness and sadness. Greater decreases of coherence during the stimulation with positive affect expressions prospectively predicted greater positive emotional responsiveness, indicated by higher amusement ratings in response to cartoons and higher scores in a questionnaire measure of exhilarability. Greater increases of coherence during the stimulation with negative affect expressions did not predict perceived funniness but were related to shorter response latencies to the amusement ratings. The results further support the notion that a more loose prefrontal-posterior coupling may be related to loosening of control of the prefrontal cortex over incoming emotional information and, thus, to a propensity to deeper emotional involvement and a greater impact of perceptual input, whereas increased prefrontal-posterior coupling may be related to strong control and the propensity to protect oneself from becoming emotionally affected.

In hospitals, the radiological services provided to non-privately insured in-house patients are mostly distributed to requesting disciplines through internal cost allocation (ICA). In many institutions, computed tomography (CT) is the modality with the largest amount of allocation credits.The aim of this work is to compare the ICA to respective DRG (Diagnosis Related Groups) shares for diagnostic CT services in a university hospital setting.The data from four CT scanners in a large university hospital were processed for the 2012 fiscal year. For each of the 50 DRG groups with the most case-mix points, all diagnostic CT services were documented including their respective amount of GOÄ allocation credits and invoiced ICA value. As the German Institute for Reimbursement of Hospitals (InEK) database groups the radiation disciplines (radiology, nuclear medicine and radiation therapy) together and also lacks any modality differentiation, the determination of the diagnostic CT component was based on the existing institutional distribution of ICA allocations.Within the included 24,854 cases, 63,062,060 GOÄ-based performance credits were counted. The ICA relieved these diagnostic CT services by € 819,029 (single credit value of 1.30 Eurocent), whereas accounting by using DRG shares would have resulted in € 1,127,591 (single credit value of 1.79 Eurocent). The GOÄ single credit value is 5.62 Eurocent.The diagnostic CT service was basically rendered as relatively inexpensive. In addition to a better financial result, changing the current ICA to DRG shares might also mean a chance for real revenues. However, the attractiveness considerably depends on how the DRG shares are distributed to the different radiation disciplines of one institution.

Background The aim of our study was to analyze the reliability of postmortem computed tomography (PMCT) versus autopsy in detecting signs of blood aspiration in a distinct group of patients following deadly head, mouth or floor of mouth gunshot injuries. Methods In this study, in 41 cases PMCT was compared to autopsy reports, the gold standard of postmortem exams, regarding detection of blood aspiration. PMCT was evaluated for the presence and level of typical signs of blood aspiration in the major airways and lung using a semi-quantitative scale ranging from level 0 (no aspiration) to 3 (significant aspiration) also taking density values of the described potential aspiratory changes into account. Results Overall, in 29 (70.7%) of 41 enrolled cases PMCT and autopsy revealed the same level of aspiration. A difference of one level between PMCT and autopsy resulted for 5 (12.2%) of the remaining 12 cases. More than one level difference between both methods resulted for 7 cases (17.2%). Autopsy described no signs of aspiration in 10 cases, compared to 31 cases with reported blood aspiration. In contrast, PMCT revealed no signs of blood aspiration in 15 cases whereas 26 cases were rated as positive for signs of aspiration in the major airways. In 18 of these 26 cases considered positive for blood aspiration by autopsy and PMCT, clear signs of aspiration signs were also described bilaterally by both methods. Conclusions The presented study provides evidence for the assumption that PMCT seems to be helpful in the detection of blood aspiration in cases of deadly head gunshots. In conclusion, it seems reasonable to suggest performing PMCT additionally to traditional postmortem exams in cases of suspected aspiration to rule out false-negative cases and to possibly allow for a more detailed and rather evidence based examination reconnoitering the cause of death. However, the adequate use of PMCT in this context needs further evaluation and the definition of an objective scale for aspiration detection on PMCT needs to be established in future studies.

The molecular basis of nonlinear optical (NLO) chiral effects in the amide I region of type I collagen was investigated using sum-frequency generation vibrational spectroscopy; chiral and achiral tensor elements were separated using different input/output beam polarization conditions. Spectra were obtained from native rat tail tendon (RTT) collagen and from cholesteric liquid crystal-like (LC) type I collagen films. Although RTT and LC collagen both possess long-range order, LC collagen lacks the complex hierarchical organization of RTT collagen. Their spectra were compared to assess the role of such organization in NLO chirality. No significant differences were observed between RTT and LC with respect to chiral or achiral spectra. These findings suggest that amide I NLO chiral effects in type I collagen assemblies arise predominantly from the chiral organization of amide chromophores within individual collagen molecules, rather than from supramolecular structures. The study suggests that sum-frequency generation vibrational spectroscopy may be uniquely valuable in exploring fundamental aspects of chiral nonlinearity in complex macromolecular structures.

High-grade glioma is the most common brain tumor in adults, and the prognosis for patients diagnosed with this type of cancer is still poor. The biological behavior of the tumors is correlated to t ...

Several immunoglobulin (IG) preparations have been approved for the immunomodulatory treatment of the neurological autoimmune diseases (AID) Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and multifocal motor neuropathy (MMN). Although efficacy has been proven in randomised clinical trials, long-term outcome data on drug utilization, effectiveness, tolerability, health related quality of life, and economic variables are lacking.In the prospective, observational internet-based SIGNS registry, patients of all age groups are eligible if they have received or are scheduled for IG therapy for neurological AID or primary or severe secondary immunodeficiency.Of the 306 patients currently included in the database (1 November 2011), 51 have neurological AID (27 males; mean age 56 ± 15 years): 21 CIDP, 7 MMN, 11 multiple sclerosis (MS), 6 myasthenia gravis, 2 myositis, 4 others (no cases of GBS). Mean duration of disease since first symptoms was 7.8 years, and disease duration since diagnosis was 5.9 years. Eight different IG preparations have been reported as current therapy. According to SF-36, patients' quality of life is substantially impaired.Present data indicate some off-label use of IG (e.g. in MS) in patients with neurological AID. Quality of life in these patients is substantially compromised. Increasing patient numbers and extended follow-up periods will provide data on treatment concepts and disease development in AID patients.

In most patients, mantle cell lymphoma (MCL) shows an aggressive clinical course with a continuous relapse pattern and a median survival of only 3-5 years. In the current study generation of the European MCL Network, the addition of high-dose Ara-C to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-like regimen followed by myeloablative consolidation achieved a significant improvement of progression-free survival in younger patients. In elderly patients, rituximab maintenance led to a marked prolongation of remission duration. Emerging strategies include mammalian target of rapamycin (mTOR) inhibitors, proteasome inhibitors, immune modulatory drugs, Bruton's tyrosine kinase inhibitors and others, all based on the dysregulated control of cell cycle machinery and impairment of several apoptotic pathways. Combination strategies are currently being investigated in numerous trials, but their introduction into clinical practice and current treatment algorithms remains a challenge. In the current survey, the application of the molecular targeted compounds were collected and evaluated by a representative national network of 14 haematological institutions. Optimised strategies are recommended for clinical routine. Future studies will apply individualised approaches according to the molecular risk profile of the patient.

In a combinatorial study numerous palladium containing mixed oxides were synthesized by a sol-gel approach and screened for their catalytic activity toward methanol synthesis from synthesis gas. Several materials exhibited higher yields than comparable supported catalysts. Titanium based materials showed to be the most promising catalytic materials, which exhibited good selectivities for temperatures below 265 °C. The materials investigated are characterized by high specific surface areas and high pore volumes which seem to have a beneficial effect on the reactivity.

Aim Outside the context of clinical trials, there is a lack of data on the management and long-term outcomes of patients with primary or secondary antibody deficiency (PID and SID), or those with neurological autoimmune diseases (AID) treated with immunoglobulins (IG).

Humane Immunglobuline (IG, uberwiegend IgG) werden zur Substitutionstherapie bei Patienten mit angeborenen (primaren) Immundefekten (PID), sowie Patienten mit sekundaren Immundefekten (SID), vor allem bedingt durch multiples Myelom oder chronisch lymphatische Leukamie angewendet. Ein weiteres Einsatzfeld besteht in der Immunmodulation bei neurologischen Autoimmunerkrankungen (NAID) wie Guillain-Barre-Syndrom, chronisch inflammatorisch demyelinisierende Polyneuropathie (CIDP) und multifokaler motorischer Neuropathie (MMN). Derzeit sind 16 IG-Praparate sind in Deutschland fur die intravenose oder subkutane Anwendung zugelassen. Aktuelle Daten zur Anwendung dieser Praparate werden derzeit in der SIGNS-Studie (Assessment of immunoglobulins in a long-term non-interventional study) in derzeit ca. 50 Studienzentren erfasst. In dieser nicht-interventionellen, prospektiven, offenen Versorgungs­forschungs­studie werden 550 Patienten mit bestehender oder neu initiierter Ig-Therapie hinsichtlich Therapiemuster (Praparatewahl, Dosierung etc.), Wirksamkeit (z. B. Infektrate bei PID und SID, Funktionalitat bei NAID), Vertraglichkeit, Lebensqualitat und Therapiekosten uber zwei Jahre beobachtet. Diese groste Studie ihrer Art soll zur Therapieoptimierung betroffener Patienten beitragen.

This study was aimed at examining the relation of an individual's EEG asymmetry in the lateral frontal cortex, assessed in resting conditions, to affective flexibility. An auditory paradigm was used to induce negative (sad) and positive (cheerful) affective states, and state-dependent shifts of dorsolateral EEG asymmetry in response to and after the emotional provocations were observed. A Left>Right activation pattern at rest was associated with a shift to the right during negative and a shift to the left during positive stimulation, and efficient recovery after negative stimulation. Right>Left participants appeared unresponsive to both sounds. Distinct and differentiated responses to provocation with negative and positive affect and efficient recovery suggest that Left>Right prefrontal activity at rest is related to a flexible pattern of affective responding, which has been linked to adaptive emotional processing in the relevant literature.

It is commonly accepted that knowledge of the degree of luminal stenosis alone is insufficient to predict a plaque’s vulnerability. Recently, several imaging techniques, such as high-resolution black-blood magnetic resonance imaging, positron emission tomography/computed tomography, ultrasound, intravascular ultrasound and computed tomography angiography, have emerged that are able to depict the arterial lumen and the vessel wall. This article will describe the potential of these imaging techniques for the identification of vulnerable plaques and will focus on the current evidence that describe the relationship between plaque imaging characterization and treatment modality selection in the coronary and carotid arteries.

Nichtmodifizierte humane Immunglobuline (IgG) sind der Standard fur die Substitutionstherapie von Patienten mit primaren (angeborenen) Immundefekten (PID) sowie sekundaren Immundefekten (SID) aufgrund von multiplem Myelom (MM) oder chronischer lymphatischer Leukamie (CLL). Auserdem werden sie zur Immunmodulation bei neurologischen Autoimmunerkrankungen wie Guillain-Barre-Syndrom (GBS), chronisch-inflammatorischer demyelinisierender Polyneuropathie (CIDP) und multifokaler motorischer Neuropathie (MMN) eingesetzt. Eine Vielzahl von IgG-Produkten steht fur die intravenose und subkutane Anwendung zur Verfugung. Hinsichtlich des breiten Indikations- und Produktspektrums sind Daten zur Anwendung in der taglichen Praxis von grosem Interesse. Auserdem werden Daten zu den Therapieergebnissen auserhalb kontrollierter klinischer Studien benotigt. Die SIGNS-Studie (Assessment of Immunoglobulins in a Long-Term Non- Interventional Study) wurde durch ein interdisziplinares klinisches Expertengremium als nichtinterventionelle, prospektive, offene Kohortenstudie (Versorgungsforschungsstudie) konzipiert. Neurologen, Padiater, Onkologen und weitere Fachgruppen schliesen in 30–40 Zentren in ganz Deutschland ca. 300 Patienten ein und werden sie uber mindestens 2 Jahre beobachten. Patienten beiderlei Geschlechts und aller Altersgruppen sind fur die Dokumentation geeignet, wenn sie zur Behandlung von PID, SID oder neurologischen Autoimmunerkrankungen IgG-Praparate erstmals oder zum wiederholten Mal erhalten und ihr schriftliches Einverstandnis erklaren. Um Selektionsbias zu minimieren, wurden keine Ausschlusskriterien definiert. Dokumentierte Parameter im Langzeitverlauf umfassen Patientencharakteristika, Anwendungsmuster (u.a. Dosierungen, Praparatewechsel), Wirksamkeit (z.B. Zahl und Schwere der Infektionen bei PID und SID), Vertraglichkeit und okonomische Variablen, um direkte Kosten erfassen zu konnen (Fehltage in Beruf und Schule, Arztbesuche). Besonderes Augenmerk liegt auf der detaillierten Erfassung der gesundheitsbezogenen Lebensqualitat und Krankheitsbelastung (u.a. bei Erwachsenen mittels SF-36, EQ-5D und WHO-5 bzw. bei Kindern mittels EQ-5D-Y, CHQ-PF-50, Kidscreen-27 und Disabkids- 37). Bei neurologischen Autoimmunerkrankungen werden u.a. Daten zur neurologischen Funktion, muskularen und physischen Funktion (Greifkraft, INCAT-Behinderungsskala etc.) und Stabilisierung/Krankheitsprogression gesammelt. Die Datenerfassung erfolgt uber eine SSL- und passwortgesicherte Internetseite und eine MySQL-Datenbank. Zur Sicherung der Datenqualitat werden Plausibilitatsprufungen bei der Dateneingabe, Ruckfragen bei den Zentren (Queries) und Monitoringbesuche durchgefuhrt. Die SIGNS-Studie soll zur Optimierung der IgG-Therapie in diesen Patientengruppen beitragen.

e18770Background: RCT are not transferable to routine care due to necessary inclusion and exclusion criteria. Thus data are needed that reflect treatment reality in routine care to decide whether r...

The Barrigao re-mobilized copper vein deposit, Iberian Pyrite Belt, southern Portugal, is located about 60 km south of Beja and 10 km southeast of the Neves Corvo ore deposit, in Alentejo Province. The deposit is structurally associated with a NE–SW striking fault zone inferred to have developed during late Variscan deformation. The copper ore itself is a breccia-type ore, characterized by up to four ore-forming stages, with the late stages showing evidence of fluid-driven element re-mobilization. The ore is dominated by chalcopyrite + tennantite-tetrahedrite, with minor arsenopyrite, pyrite, and lollingite. The supergene paragenesis is composed mainly of bornite, covellite, and digenite. Whole-rock analyses show anomalous tin and germanium contents, with averages of 320 and 61 ppm, respectively. Electron microprobe analysis of Barrigao ores revealed the germanium and tin to be restricted to chalcopyrite, which underwent late-stage hydrothermal fluid overprint along distinct vein-like zones. The measured ...

Though government intervention is prevalent in the market for research and development (R&D), most literature has focused on the use of subsidies, patents or joint research ventures to obtain the efficient R&D investment. By using a two-stage duopoly model in which firms first choose the level of investment and then output, our paper shows that the introduction of a price ceiling by the regulator will result in the optimal level of R&D. This interesting but counterintuitive result contrasts with the existing literature and advances our understanding about price ceilings.

The influence of different dopants in varying contents on the activity and selectivity of Ni-based methanation catalysts under proton exchange membrane fuel cell (PEMFC) relevant conditions (hydrogen-rich gas reformate with low concentrations of CO and excess CO2) was investigated. The modification of Ni100Ox with 2.2 mol% of Re resulted in a catalyst highly inactive for both the methanation of CO and CO2 while the addition of Zr led to an enhanced CO and CO2 methanation activity. Further modification of Zr10Ni90Ox with small amounts of Re caused a drastically decreased reactivity towards the undesired hydrogenation of CO2 while that for CO was practically unchanged. Solo methanation experiments unambiguously reveal that this increase in selectivity is based on a loss of the intrinsic CO2 reactivity and not necessarily associated with any competition for active sites between the different kinds of carbon oxides. A detailed study of the impact of the compositional variations on structural and chemical properties was performed using nitrogen physisorption, hydrogen chemisorption, temperature-programmed reduction (TPR), temperature-programmed desorption experiments of CO2 (CO2 TPD), X-ray diffraction (XRD), X-ray photoelectron spectra (XPS) as well as TEM. As a part of the catalytically active Ni particles, Re changes the surface of the catalyst resulting in drastically altered catalytic properties while Zr or the Ni–ZrO2 interfacial region seems to play a decisive role in the activation of the CO molecule.

Using a human TSH receptor (TSH-R) cDNA probe we investigated TSH-R expression levels in 20 human thyroid fragments by Northern blot analysis: 14 Graves' disease, 2 Hashimoto's disease, 3 endemic goiter and 1 healthy thyroid gland. TSH-R expression was low in those thyroids where expression of the major histocompatibility complex class I (MHC I), class II (MHC II) and intercellular adhesion molecule 1 (ICAM-1) was high, whereas expression of the endothelial leukocyte adhesion molecule 1 (ELAM-1) bore no relation to TSH-R expression. In situ hybridization showed that next to lymphocytes (MHC II), thyroid cells (MHC II, ICAM-1) and endothelial cells (ICAM-1, ELAM-1) were the source of transcripts of these T-cell activating antigens. We conclude that next to MHC I and II, the expression of additional T-cell activating antigens such as ICAM-1 and ELAM-1 play a role in the initiation of auto-immune thyroid disease.

BACKGROUND The petromastoid canal was first described in 1904 by Mouret and Rouviere. Since then, there have been very few publications about this canal. Modern high-resolution computed tomography (CT) enables a slice thickness of 1 mm and less, so the course of the petromastoid canal is visible. In this study the petromastoid canal is introduced and its dimensions measured. MATERIALS AND METHODS This study involved 316 CT scans of normal temporal bones of subjects age 19.6-84.2: 156 temporal bones of women and 160 temporal bones of men. The slice thickness of the CT scan was 0.5 mm, and 16-slice or 64-slice CT was used. The middle diameter, length, and angle of the petromastoid canal were measured. RESULTS The middle diameter of the petromastoid canal was 1.16+/-0.4 mm (0.25-2.5 mm), the length was 10.7+/-0.9 mm (4.25-16.1 mm), and the angle was 134.5+/-17.3 degrees (124-157 degrees). CONCLUSION The study shows for the first time the length and angle of the petromastoid canal. A slice thickness of at least 1 mm guarantees 100% imaging of the petromastoid canal. The petromastoid canal is an important anatomical landmark and is of clinical relevance.

Mechanical stress is one of the risk factors believed to influence intervertebral disc degeneration. Animal models have shown that certain regimes of compressive loading can induce a cascade of biological effects that ultimately results in cellular and structural changes in the disc. It has been proposed that both cell-mediated breakdown of collagen and the compromised stability of collagen with loss of anular tension could result in degradation of lamellae in the anulus fibrosus (AF). To determine whether this may be important in the AF, we subjected entire rings of de-cellularized AF tissue to MMP-1 digestion with or without tension. Biomechanical testing found trends of decreasing strength and stiffness when tissues were digested without tension compared with those with tension. To determine the physiologic significance of tissue level tension in the AF, we used an established in vivo murine model to apply a disc compression insult known to cause degeneration. Afterward, that motion segment was placed in fixed-angle bending to impose tissue level tension on part of the AF and compression on the contralateral side. We found that the AF on the convex side of bending retained a healthy lamellar appearance, while the AF on the concave side resembled tissues that had undergone degeneration by loading alone. Varying the time of onset and duration of bending revealed that even a brief duration applied immediately after cessation of compression was beneficial to AF structure on the convex side of bending. Our results suggest that both cell-mediated events and cell-independent mechanisms may contribute to the protective effect of tissue level tension in the AF.

PURPOSE: The purpose of this study was to compare color coded duplex sonography (CCDS), contrast-enhanced ultrasound (CEUS) and multislice computed tomography (MS-CT) angiography in pathological aortic lesions. MATERIAL AND METHODS: 36 patients with a mean age of 71 years (range 51-87 yrs) with known or suspected treated and untreated aortic lesions detected by CTA were included in this prospective study. Standardized MS-CTA using a 16 or 64 row scanner (Somatom Sensation 16 or 64, Siemens Medical Systems, Forchheim, Germany) served as reference standard. The patients were examined with CCDS and CEUS (Logiq 9, General Electrics, Milwaukee, WI) using the low MI technique with intravenous injection of 1.6-2.4 ml SonoVue (Bracco, Italy). Contrast enhanced ultrasound was performed in the arterial, venous and late venous phase. RESULTS: In all patients CEUS resulted in a relevant diagnosis of an aortic pathology. In total, two covered ruptures, nine aortic dissections and five aortic aneurysms were detected. In the routine follow-up of 20 patients following endovascular repair (EVAR) of abdominal aortic aneurysm (AAA), one type 3 and three type 2 endoleaks after y-stent graft were detected. For presurgical planning, in addition to the perfused true and false lumen after dissection the perfusion of the renal arteries was examined. CONCLUSION: CEUS with SonoVue allows the evaluation of aortic lesions. It is an additional examination to CTA. It may allow a more rapid and noninvasive diagnosis, especially in critical patients from intensive care units because of its bedside availability. As the examination is dynamic, additional information about blood flow in the true and false lumen and about renal perfusion after dissections can be evaluated. Especially in patients with contraindications to CT contrast agents (e.g. due to renal failure or severe allergy), CEUS provides a good alternative to MS-CT.

To evaluate the effectiveness of contrast-enhanced ultrasound (CEUS) in the diagnosis and characterization of hepatic, renal and splenic traumatic injuries versus conventional ultrasound (US) and multislice computed tomography (MS-CT). Between January 2005 and January 2007, 78 patients (48 males, 30 females, mean age 56 years) with blunt abdominal trauma were examined by conventional US, CEUS and MS-CT. CEUS employed a low-MI technique using 1.2 to 2.4 ml of SonoVue (Bracco, Italy) i.v. and a multifrequency transducer (2-4 MHz, Siemens, Sequoia, Acuson). CT examinations were performed on a 64 detector CT scanner (Somatom Sensation 16 or 64, Siemens Medical Systems, Forchheim, Germany) before and after administration of 120 ml intravenous contrast agent (Solutrast®, Bracco, Milan, Italy) followed by 50 ml saline. The presence of hepatic, renal and splenic injuries was analyzed and the conspicuousness of findings was assessed. In 15 of the 78 patients conventional US identified solid organ injuries: 8 hepatic, 2 renal and 5 splenic injuries. CEUS identified 3 more injuries (2 hepatic and 1 splenic) that had been missed by conventional US. CEUS identified traumatic lesions in 18/78 patients. In one of the 18 patients even active bleeding could be identified by CEUS. In CEUS solid organ injuries appeared hypoechoic. MS-CT identified 18 solid organ injuries in 78 patients, corroborating the CEUS results. CEUS greatly improves the visualization and characterization of hepatic, renal and splenic injuries compared to conventional ultrasound and correlates well with MS-CT. The imaging technique detects even minor blood flow and is able to depict vascular structures in detail. At our institution it is used as an additional examination technique which supplements MS-CT in unclear cases. Owing to its bedside availability, CEUS provides a good alternative to MS-CT, especially in patients with contraindications to CT contrast agents (e.g. due to renal failure or severe allergy) and in hemodynamically compromised patients.

Objectives: The primary purpose of this study was to describe individuals' knowledge and beliefs about genetics and smoking. Secondary purposes were to describe (a) differences in knowledge and beliefs based on smoking status, gender, and education and (b) relationships among perceived genetic predisposition for smoking, background characteristics, and knowledge and beliefs about genetics and smoking. Because genetics influences smoking, genetic information will likely be used to individualize future cessation treatment. Design: Questionnaire data were collected about knowledge and beliefs about genetics and smoking, smoking history, and demographics from visitors and staff at a nursing care facility. Data were analyzed with bivariate statistics and logistic regression. Sample: Participants (N=92), ages 19–82, were classified by smoking status. Results: Participants had little knowledge about genetics and smoking or mechanisms of heredity. Most did not believe that genetics caused smoking or influenced cessation. Predictors of perceived genetic predisposition for smoking were smoking status (current/former smoker), education (

BACKGROUND AND OBJECTIVE: Data for quality of care and health economics in patients with occupationally acquired hepatitis C are lacking in Germany. The aim of this study was to analyse quality and economics of health care in occupationally acquired hepatitis C recognized by the Employees Compensation Boards between 1993 and 2000 in the area of Cologne and Bochum, Germany. METHODS: Results for 192 patients (146 women and 46 men, mean age 42 +/- 10 years) were analysed, using a standardized evaluation form. In addition to direct medical costs and diagnostic and therapeutic performance, disability days and benefit payments were also analysed. The observational period was from 01.01.1993 to 31.07.2004. Disability benefits were considered from 1983 onwards. RESULTS: HCV genotype 1 accounted for 79 % of infections. 112 patients (58 %) received antiviral treatment at least once. There were no differences in treatment rates between patients with prognostically favorable genotypes (2/3) and those with unfavorable HCV types (1/4) (59 % v. 60 %) or patients with low and those with advanced fibrosis (61 % v. 64 %). A sustained virological response was achieved in 53 % of treated patients. Disability days were more frequent in patients receiving antiviral treatment (214 v. 67 days). The cost of medication made up a major part of health care expenditure (mean of i 13,279 per patient). In addition, total disability benefits of i 6,933,789 were paid out between 1983 and 2004. CONCLUSION: Occupationally acquired hepatitis C is a major health-economic burden in Germany. Quality of health care corresponded to guidelines at any one time and sustained virological response was in the range of large controlled trials. However, 69 % of the patients remain chronically infected and are at risk for disease progression and transmission.

FDG-PET/CT examinations combine metabolic and morphologic imaging within an integrated procedure. Over the past decade PET/CT imaging has gained wide clinical acceptance in the field of oncology. This FDG-PET/CT guideline focuses on indications, data acquisition and processing as well as documentation of FDG-PET/CT examinations in oncologic patients within a clinical and social context specific to Germany. Background information and definitions are followed by examples of clinical and research applications of FDG-PET/CT. Furthermore, protocols for CT scanning (low dose and contrast-enhanced CT) and PET emission imaging are discussed. Documentation and reporting of examinations are specified. Image interpretation criteria and sources of errors are discussed. Quality control for FDG and PET/CT-systems, qualification requirements of personnel as well as legal aspects are presented.

The cost-effectiveness of rituximab in combination with fludarabine/cyclophosphamide (R-FC) for the first line treatment of chronic lymphocytic leukemia (CLL) was evaluated. Based on long-term clinical data (follow-up of 5.9 years) from the CLL8-trial, a Markov-model with three health states (Free from disease progression, Progressive disease, Death) was used to evaluate the cost per quality-adjusted life-year (QALY) and cost per life years gained (LYG) of R-FC from the perspective of the German statutory health insurance (SHI). The addition of rituximab to FC chemotherapy results in a gain of 1.1 quality-adjusted life-years. The incremental cost-effectiveness ratio (ICER) of R-FC compared with FC was €17,979 per QALY (€15,773 per LYG). Results were robust in deterministic and probabilistic sensitivity analyses. From the German SHI perspective, rituximab in combination with FC chemotherapy represents good value for first-line treatment of patients with CLL and compares favorably with chemotherapy alone.

Male breast cancer (MBC) is unusual, especially in young adults. Most cases of MBC as a secondary malignancy relate to the previous treatment with ionizing radiation. MBC can be associated with mutations in hereditary cancer predisposition syndrome genes (i.e., BRCA2); however, no such association has been reported in patients with Cowden syndrome (involving the phosphatase and tensin homolog [PTEN] gene). We describe a patient with Cowden syndrome who was initially diagnosed with B-cell lymphoblastic lymphoma at the age of 7 years, then MBC at the age of 31 years, and never received radiation therapy.

This article discusses the morphological criteria for the differentiation between acute osteoporotic and metastatic vertebral body fractures and new imaging methods, such as diffusion-weighted and chemical shift magnetic resonance imaging (MRI) are presented.The differential diagnostics of osteoporotic and metastatic vertebral body fractures can be difficult in some cases. Both entities normally occur without adequate trauma and predominantly in elderly patients.Conventional X-ray examination is the initial imaging method of choice but is not able to reliably differentiate between the osteoporotic or metastatic etiology of a fracture. Computed tomography (CT) clearly depicts osseous destruction in metastatic fractures but lacks specificity. Magnetic resonance imaging (MRI) shows a higher sensitivity and specificity in differentiating osteoporotic and metastatic fractures.The combination CT and MRI allows an accurate diagnosis with respect to an osteoprorotic or metastatic etiology in most of cases but bone marrow edema in acute fractures sometimes leads to ambiguous results and differential diagnostic problems.

Background/Aims: Therapeutic options for hepatitis C non-responder patients are limited. Methods: We initiated an open-label pilot study to investigate the efficacy of CIFN plus ribavirin on viral kinetics, sustained virological response (SVR), and histological response in hepatitis C non-responder patients. Seventy-seven patients were enrolled to receive CIFN given daily in combination with 1000/1200 mg ribavirin. An 8-week inductiondosing regimen of 18 mg CIFN, followed by 9 mg for 40 weeks was compared to 9 mg CIFN for 48 weeks. 90% of patients were infected with HCV-genotype 1. Results: Overall, 82% of the patients demonstrated an early virological response, 65% had an end-of-treatment response, and the SVR was 30%. Interferon/ribavirin non-responders demonstrated a SVR of 22%. Induction-dosing resulted in a greater first-phase HCV-RNA decay that, however, did not translate to better SVRs, presumably due to more dose modifications. High ALT, younger age, and second-phase viral kinetics were associated with SVR. Only sustained responders and relapse patients showed an improved liver histology. Conclusions: Daily dosing of CIFN plus ribavirin may be a promising concept for selected non-responder patients before considering therapies which are anti-viral but not curative. However, motivation and compliance are requisites and a CIFN induction is not required. q 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PURPOSE: Retrospective analysis of the success and complication rates of chest port implantation via the lateral subclavian vein. MATERIALS AND METHODS: Between January 2003 and June 2004, the lateral subclavian vein in 271 patients (186 women, 85 men, mean age 53.2 years) was punctured guided by ultrasound. This access was used to insert a port system, and the catheter tip was placed at the cavoatrial junction. The port reservoir was implanted in a subcutaneous infraclavicular pocket and fixed to the fascia of the pectoralis muscle. Indications for port implantation were chemotherapy (n = 239), total parenteral nutrition (n = 2) and intravenous medication (n = 30). The patient follow-up was mainly performed either by the oncology division of the department of gynecology or by the department of internal medicine. RESULTS: A chest port catheter system was successfully implanted in all patients. The catheter remained in place for a mean duration of 269.4 days (SD 192.3 days). No complications occurred during implantation. In the post-interventional period, 6 catheter dysfunctions were found (thrombotic 0.09 per 1000 catheter days; mechanic 0.05 per 1000 catheter days). While one local infection occurred in the early post-interventional period, 3 local and 15 systemic infections were independent of the port catheter placement (0.39 per 1000 catheter days). The rate of port catheter ex-plantation due to dysfunction or infection was 0.07 per 1000 catheter days. CONCLUSION: Ultrasound-guided puncture of the lateral subclavian vein is a safe procedure for the insertion of central venous port catheter systems and had a very low complication rate in our study. For further evaluation of our port placement technique, prospective studies compared to placement through the internal jugular vein are necessary.

BILN-2061, a specific and potent peptidomimetic inhibitor of the HCV NS3 protease, has recently been shown to markedly lower serum hepatitis C virus (HCV)-RNA levels in patients chronically infected with HCV genotype 1 in three 2-day proof of principle studies. The aim of the current study was to assess the antiviral efficacy of BILN-2061 in patients with genotypes 2 and 3 HCV infection. The antiviral efficacy, pharmacokinetics, and tolerability of 500 mg twice-daily BILN-2061 given as monotherapy for 2 days in 10 patients chronically infected with non–genotype 1 HCV (genotype 2: n = 3; genotype 3: n =7) and minimal liver fibrosis (Ishak score 0-2) were assessed in a placebo-controlled (placebo n = 2), double-blind pilot study. HCV-RNA levels decreased by ≥1 log10 copies/mL in 4 of 8 patients treated with BILN-2061. One patient showed a weak response of

The risk for cardiovascular disease in diabetes is excessive. Multislice spiral computed tomography (MSCT) is a new technique for the assessment of coronary calcification in coronary artery disease. The aim of the study was to evaluate the presence of coronary calcium in asymptomatic long-term type 1 diabetic patients. Seventy-one type 1 diabetic patients (age 48 +/- 9 y, HbA1c 7.7 +/- 1.2, BMI 24.4 +/- 2.8, duration of diabetes 26 +/- 9 y) without clinical evidence for coronary artery disease were assessed with MSCT. A volumetric score was used to calculate the coronary calcification (CC) score. Five cardiac reflex tests were performed to study patients for cardiac autonomic neuropathy. Coronary calcifications were detectable in 22 (31 %) type 1 diabetic patients (CC-score > 0, mean CC-score 174 +/- 228 [X+/-SD]). Fourty-nine (69 %) type 1 diabetic patients demonstrated no coronary calcifications (CC-score= 0). In patients with coronary calcifications, both cardiac autonomic neuropathy and retinopathy were detected more frequently than in those without (64 % vs. 29 %, p < 0.02; 59 % vs. 31 %; p < 0.02). Duration of diabetes was longer in patients with than without coronary calcification (32 +/- 10 y vs. 24 +/- 8 y, p < 0.01). Age, BMI, and HbA1c were not significantly different between patients with and without coronary calcification. The study demonstrates that nearly one third of asymptomatic long-term type 1 diabetic patients present with coronary calcifications. In the patients, there is evidence for an association between coronary calcification and both cardiac autonomic neuropathy and retinopathy. MSCT is a promising non-invasive approach to analyze early alterations of the coronary system in diabetic patients.

BACKGROUND Endoscopic ultrasound (EUS)-guided fine-needle aspiration biopsy (EUS-FNA) is increasingly used for the diagnosis of malignant and benign disease in the region of the upper GI tract. We prospectively investigated the clinical accuracy and safety of this method in unselected patients under routine conditions. PATIENTS AND METHODS 101 consecutive patients (median 61.5 years; 56 female) were enrolled in the study, in whom a total of 106 tissue biopsies were obtained by using EUS-FNA. Major indications for EUS-FNA were suspicious lesions located in the mediastinum, esophagus, stomach, pancreas, liver, biliary system, adrenals or retroperitoneum. A longitudinal echoendoscope (HITACHI FG-34UX) equipped with a standard 22G -aspiration needle was used. The aspirated specimens were analyzed further by using standard cytology and/or histology. Lymph-node biopsies were additionally subjected to flow-cytometry (FACS-light-chain restriction). Surgery was used for reference (where available). In the remaining cases the final diagnosis obtained by the clinical course and all available imaging and histologic informations (ultrasound, CT, MRT) was used for reference. RESULTS EUS-FNA caused no serious complications. In 6/106 specimen (5.6 %) no sufficient cell material could be aspirated. In the remaining 100 specimens EUS-FNA reached an overall sensitivity of 78 % and a specificity of 100 %, while the accuracy was 89 % and the positive and negative predictive values were 100 % and 81 %, respectively. The greatest diagnostic accuracy was achieved in mediastinal and retroperitoneal lesions, while the accuracy of EUS-FNA in pancreatic lesions and perigastric lymph nodes was distinctly smaller (

Background and Study Aims: EUS-guided fine-needle aspiration biopsy (EUS-FNA) is used increasingly for the diagnosis of mediastinal, biliopancreatic, and gastric tumors. However, little is known about EUS-FNA in hepatic lesions and the best method for tissue analysis. We assessed EUS-FNA combined with histological and cytological evaluation in selected patients. Patients and Methods: 41 patients (66 ′ 7 years) were prospectively studied, 33 of whom had clinical findings suggestive ofliver malignancies. Selection for EUS-FNA was based on an increased risk of bleeding from percutaneous biopsy (coagulopathy, cirrhosis, ascites, aspirin intake; n = 15), presence of small liver tumors < 2 cm (n = 12), or liver lesions found incidentally (n = 14). Transgastric EUS-FNA of lesions located in accessible liver segments was performed using the Hitachi FG-34UX longitudinal echo endoscope and a 22-G aspiration needle. Specimens were submitted separately for standard cytological and histological evaluation. In the case of malignancies, findings at surgery with histological examination, endoscopy, or computed tomography (CT)-guided biopsy of the primary cancer served as reference results (n = 33), while in benign disorders, a combination of imaging studies (Magnetic Resonance Tomography [MRT], scintigraphy) and the clinical follow-up, as summarized in the physician's report, was used as reference. Results: EUS-FNA provided appropriate biopsy specimens in 40/ 41 patients. It was not possible to aspirate sufficient material in one patient. On average, 1.4 needle passes were necessary to obtain sufficient amounts of tissue. With regard to malignancy, the combination of histological and cytological examination had a sensitivity of 94%, specificity of 100%, negative predictive value (NPV) of 78%, and positive predictive value (PPV) of 100%. Tissue diagnoses were in agreement in 27/41 patients (65%). In the remaining patients, only the cytological examination identified six lesions correctly, while the histological assessment was correct in another seven patients. Malignant lesions were correctly identified by cytology in 24/33 (73%) patients, while histology alone was diagnostic for malignancy in 27/33 (82%) patients. When both modalities were combined, 31 out of 33-malignancies (94%) were correctly diagnosed. Minor complications occurred in two patients and consisted of self-limiting local bleeding. Conclusions: EUS-FNA of liver tumors is a powerful, reliable, and safe procedure for the diagnosis of malignant liver lesions. Optimal diagnostic results are achieved by combining cytological with histological assessment. Hence, EUS-FNA is an alternative to percutaneous biopsy, particularly in patients at risk of bleeding or with small lesions of the liver.

Collagen possesses a strong second-order nonlinear susceptibility, a nonlinear optical property characterized by second harmonic generation in the presence of intense laser beams. We present a new technique involving polarization modulation of an ultra-short pulse laser beam that can simultaneously determine collagen fiber orientation and a parameter related to the second-order nonlinear susceptibility. We demonstrate the ability to discriminate among different patterns of fibrillar orientation, as exemplified by tendon, fascia, cornea, and successive lamellar rings in an intervertebral disc. Fiber orientation can be measured as a function of depth with an axial resolution of approximately 10 microm. The parameter related to the second-order nonlinear susceptibility is sensitive to fiber disorganization, oblique incidence of the beam on the sample, and birefringence of the tissue. This parameter represents an aggregate measure of tissue optical properties that could potentially be used for optical imaging in vivo.