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We present the case of a 41-year-old woman who was admitted to our centre with progressive symptoms of congestive heart failure (NYHA class III) 5 years after a radical nephrectomy for renal cell carcinoma. Magnetic resonance imaging demonstrated a 5 x 3 cm homogeneous intracardial mass causing right ventricular outflow tract obstruction, not accessible to surgical resection. Serial echo-guided, percutaneous coil embolization of the cardial metastasis was performed with Contour SE Microparticles (150-250 or 300-500 microm) after identification of the target region of the metastasis by contrast injection (Levovist) through the balloon catheter into the coronary artery under transoesophageal echocardiographic control prior to induction of the necrosis, corresponding to the technique which has been described for septal ablation in hypertrophic obstructive cardiomyopathy. Follow-up after serial embolization showed a good haemodynamic and a marked clinical response (dyspnoea NYHA I-II) which lasted during the 19 month of survival after the index procedure. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS), a neuroinflammatory disorder, occurs as non-progressive or progressive phenotypes; both forms present with diverse symptoms that may reduce quality of life (QoL). Adherence to healthy lifestyle behaviors has been associated with higher QoL in people with MS; whether these associations differ based on MS phenotype is unknown. Cross-sectional self-reported observational data from 1108 iConquerMS participants were analysed. Associations between lifestyle behaviors and QoL were assessed by linear regression, and phenotype differences via moderation analyses. Diet, wellness, and physical activity, but not vitamin D or omega-3 supplement use, were associated with QoL. Specifically, certain diet types were negatively associated with QoL in relapsing-remitting MS (RRMS), and positively associated in progressive MS (ProgMS). Participation in wellness activities had mixed associations with QoL in RRMS but was not associated in ProgMS. Physical activity was positively associated with QoL in RRMS and ProgMS. Phenotype differences were observed in diet and wellness with physical QoL, and physical activity with most QoL subdomains. Our findings show lifestyle behaviors are associated with QoL and appear to differ based on MS phenotype. Future studies assessing timing, duration, and adherence of adopting lifestyle behaviors may better inform their role in MS management.

Background: Many individuals with multiple sclerosis (MS) depart the workforce prematurely. In the United States, access to insurance, including health, disability income, long-term care, and life insurance, is largely employment-based or purchased from earnings. Many individuals we see in the clinic experience financial hardship because of a lack of insurance, even if working. We sought to determine the proportion of workers who are financially protected through insurance coverage and the sources of this coverage in a large sample., Methods: We developed an online survey and opened it to individuals aged 18 to 65 years registered with the North American Research Committee on Multiple Sclerosis, iConquerMS, or the National Multiple Sclerosis Society Minority Advisory Council. Data collected included demographic and disease characteristics, current information about each insurance type (coverage vs no coverage), and when the current insurance policies were obtained relative to MS diagnosis., Results: Of 2507 survey respondents, 82.9% were female, 3.8% Hispanic/Latino, and 91.2% White. The mean ± SD age was 53.5 ± 8.5 years and disease duration was 16.4 ± 8.5 years after diagnosis. The most frequently held insurance types were health (96.3%) and life (58.8%). Only 9.7% of respondents had long-term care insurance. Except for life insurance, most current policies were obtained after MS diagnosis., Conclusions: Individuals with MS might not prioritize the possible short- and long-term benefits of these types of insurance. Health care providers can direct patients to nonprofit agencies that educate about of these insurance types and emphasize that others with MS have obtained these insurance types after their diagnosis., Competing Interests: Financial Disclosures: Dr Miller has contributed to intellectual property that is a part of the Multiple Sclerosis Performance Test, for which she has the potential to receive royalties. Dr Cofield has been compensated for being a grant reviewer for the Department of Defense. Dr Planchon has received research funding from the Guthy-Jackson Charitable Foundation. The other authors declare no conflicts of interest., (© 2021 Consortium of Multiple Sclerosis Centers.)

Awareness of various arguments can help interactants present opinions, stress points, and build counterarguments during discussions. At school, some topics are taught in a way that students learn to accumulate knowledge and gather arguments, and later employ them during debates. Prior knowledge may facilitate recalling information on well structured, fact-based topics, but does it facilitate recalling arguments during discussions on complex, interdisciplinary topics? We assessed the prior knowledge in domains related to a bioethical topic of 277 students from Germany (approximately 15 years old), their interest in the topic, and their general knowledge. The students read a text with arguments for and against prenatal diagnostics and tried to recall the arguments one week later and again six weeks later. Prior knowledge in various domains related to the topic individually and separately helped students recall the arguments. These relationships were independent of students' interest in the topic and their general knowledge., (Copyright © 2017 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

While next-generation sequencing (NGS) has become the primary technology for discovering gene fusions, we are still faced with the challenge of ensuring that causative mutations are not missed while minimizing false positives. Currently, there are many computational tools that predict structural variations (SV) and gene fusions using whole genome (WGS) and transcriptome sequencing (RNA-seq) data separately. However, as both WGS and RNA-seq have their limitations when used independently, we hypothesize that the orthogonal validation from integrating both data could generate a sensitive and specific approach for detecting high-confidence gene fusion predictions. Fortunately, decreasing NGS costs have resulted in a growing quantity of patients with both data available. Therefore, we developed a gene fusion discovery tool, INTEGRATE, that leverages both RNA-seq and WGS data to reconstruct gene fusion junctions and genomic breakpoints by split-read mapping. To evaluate INTEGRATE, we compared it with eight additional gene fusion discovery tools using the well-characterized breast cell line HCC1395 and peripheral blood lymphocytes derived from the same patient (HCC1395BL). The predictions subsequently underwent a targeted validation leading to the discovery of 131 novel fusions in addition to the seven previously reported fusions. Overall, INTEGRATE only missed six out of the 138 validated fusions and had the highest accuracy of the nine tools evaluated. Additionally, we applied INTEGRATE to 62 breast cancer patients from The Cancer Genome Atlas (TCGA) and found multiple recurrent gene fusions including a subset involving estrogen receptor. Taken together, INTEGRATE is a highly sensitive and accurate tool that is freely available for academic use., (© 2016 Zhang et al.; Published by Cold Spring Harbor Laboratory Press.)

Large-scale cancer sequencing data enable discovery of rare germline cancer susceptibility variants. Here we systematically analyse 4,034 cases from The Cancer Genome Atlas cancer cases representing 12 cancer types. We find that the frequency of rare germline truncations in 114 cancer-susceptibility-associated genes varies widely, from 4% (acute myeloid leukaemia (AML)) to 19% (ovarian cancer), with a notably high frequency of 11% in stomach cancer. Burden testing identifies 13 cancer genes with significant enrichment of rare truncations, some associated with specific cancers (for example, RAD51C, PALB2 and MSH6 in AML, stomach and endometrial cancers, respectively). Significant, tumour-specific loss of heterozygosity occurs in nine genes (ATM, BAP1, BRCA1/2, BRIP1, FANCM, PALB2 and RAD51C/D). Moreover, our homology-directed repair assay of 68 BRCA1 rare missense variants supports the utility of allelic enrichment analysis for characterizing variants of unknown significance. The scale of this analysis and the somatic-germline integration enable the detection of rare variants that may affect individual susceptibility to tumour development, a critical step toward precision medicine.

Prior knowledge is known to facilitate learning new information. Normally in studies confirming this outcome the relationship between prior knowledge and the topic to be learned is obvious: the information to be acquired is part of the domain or topic to which the prior knowledge belongs. This raises the question as to whether prior knowledge of various domains facilitates recalling information. In this study 79 eleventh-grade students completed a questionnaire on their prior knowledge of seven different domains related to the bioethical dilemma of prenatal diagnostics. The students read a text containing arguments for and arguments against prenatal diagnostics. After 1 week and again 12 weeks later they were asked to write down all the arguments they remembered. Prior knowledge helped them recall the arguments 1 week (r = 0.350) and 12 weeks (r = 0.316) later. Prior knowledge of three of the seven domains significantly helped them recall the arguments 1 week later (correlations between r = 0.194 and 0.394). Partial correlations with interest as a control item revealed that interest did not explain the relationship between prior knowledge and recall. Prior knowledge of different domains jointly supports the recall of arguments related to bioethical topics.

Several genetic alterations characteristic of leukemia and lymphoma have been detected in the blood of individuals without apparent hematological malignancies. The Cancer Genome Atlas (TCGA) provides a unique resource for comprehensive discovery of mutations and genes in blood that may contribute to the clonal expansion of hematopoietic stem/progenitor cells. Here, we analyzed blood-derived sequence data from 2,728 individuals from TCGA and discovered 77 blood-specific mutations in cancer-associated genes, the majority being associated with advanced age. Remarkably, 83% of these mutations were from 19 leukemia and/or lymphoma-associated genes, and nine were recurrently mutated (DNMT3A, TET2, JAK2, ASXL1, TP53, GNAS, PPM1D, BCORL1 and SF3B1). We identified 14 additional mutations in a very small fraction of blood cells, possibly representing the earliest stages of clonal expansion in hematopoietic stem cells. Comparison of these findings to mutations in hematological malignancies identified several recurrently mutated genes that may be disease initiators. Our analyses show that the blood cells of more than 2% of individuals (5-6% of people older than 70 years) contain mutations that may represent premalignant events that cause clonal hematopoietic expansion.

We report the first large-scale exome-wide analysis of the combined germline-somatic landscape in ovarian cancer. Here we analyse germline and somatic alterations in 429 ovarian carcinoma cases and 557 controls. We identify 3,635 high confidence, rare truncation and 22,953 missense variants with predicted functional impact. We find germline truncation variants and large deletions across Fanconi pathway genes in 20% of cases. Enrichment of rare truncations is shown in BRCA1, BRCA2 and PALB2. In addition, we observe germline truncation variants in genes not previously associated with ovarian cancer susceptibility (NF1, MAP3K4, CDKN2B and MLL3). Evidence for loss of heterozygosity was found in 100 and 76% of cases with germline BRCA1 and BRCA2 truncations, respectively. Germline-somatic interaction analysis combined with extensive bioinformatics annotation identifies 222 candidate functional germline truncation and missense variants, including two pathogenic BRCA1 and 1 TP53 deleterious variants. Finally, integrated analyses of germline and somatic variants identify significantly altered pathways, including the Fanconi, MAPK and MLL pathways.

Producing gene fusions through genomic structural rearrangements is a major mechanism for tumor evolution. Therefore, accurately detecting gene fusions and the originating rearrangements is of great importance for personalized cancer diagnosis and targeted therapy. We present a tool, BreakTrans, that systematically maps predicted gene fusions to structural rearrangements. Thus, BreakTrans not only validates both types of predictions, but also provides mechanistic interpretations. BreakTrans effectively validates known fusions and discovers novel events in a breast cancer cell line. Applying BreakTrans to 43 breast cancer samples in The Cancer Genome Atlas identifies 90 genomically validated gene fusions. BreakTrans is available at http://bioinformatics.mdanderson.org/main/BreakTrans.

Most mutations in cancer genomes are thought to be acquired after the initiating event, which may cause genomic instability and drive clonal evolution. However, for acute myeloid leukemia (AML), normal karyotypes are common, and genomic instability is unusual. To better understand clonal evolution in AML, we sequenced the genomes of M3-AML samples with a known initiating event (PML-RARA) versus the genomes of normal karyotype M1-AML samples and the exomes of hematopoietic stem/progenitor cells (HSPCs) from healthy people. Collectively, the data suggest that most of the mutations found in AML genomes are actually random events that occurred in HSPCs before they acquired the initiating mutation; the mutational history of that cell is "captured" as the clone expands. In many cases, only one or two additional, cooperating mutations are needed to generate the malignant founding clone. Cells from the founding clone can acquire additional cooperating mutations, yielding subclones that can contribute to disease progression and/or relapse., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Attempts at depositing uniform films of nanoparticles by drop-drying have been frustrated by the "coffee-stain" effect due to convective macroscopic flow into the contact line. Here, we show that uniform deposition of nanoparticles in aqueous suspensions can be attained easily by drying the droplet in an ethanol vapor atmosphere. This technique allows the particle-laden water droplets to spread on a variety of surfaces such as glass, silicon, mica, PDMS, and even Teflon. Visualization of droplet shape and internal flow shows initial droplet spreading and strong recirculating flow during spreading and shrinkage. The initial spreading is due to a diminishing contact angle from the absorption of ethanol from the vapor at the contact line. During the drying phase, the vapor is saturated in ethanol, leading to preferential evaporation of water at the contact line. This generates a surface tension gradient that drives a strong recirculating flow and homogenizes the nanoparticle concentration. We show that this method can be used for depositing catalyst nanoparticles for the growth of single-walled carbon nanotubes as well as to manufacture plasmonic films of well-spaced, unaggregated gold nanoparticles.

There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in cerebrospinal fluid (CSF) are being used in clinical practice. Anti-aquaporin-4 antibodies in serum are currently useful for the diagnosis of neuromyelitis optica (NMO), but we could expect novel CSF biomarkers that help define prognosis and response to treatment for this disease. One of the most critical factors in biomarker research is the inadequate powering of studies performed by single centers. Collaboration between investigators is needed to establish large biobanks of well-defined samples. A key issue in collaboration is to establish standardized protocols for biobanking to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by pre-analytical factors. Here, consensus guidelines for CSF collection and biobanking are presented, based on the guidelines that have been published by the BioMS-eu network for CSF biomarker research. We focussed on CSF collection procedures, pre-analytical factors and high quality clinical and paraclinical information. Importantly, the biobanking protocols are applicable for CSF biobanks for research targeting any neurological disease.

We study the solubility and dispersibility of as-produced and purified HiPco single-walled carbon nanotubes (SWNTs). Variation in specific operating conditions of the HiPco process are found to lead to significant differences in the respective SWNT solubilities in oleum and surfactant suspensions. The diameter distributions of SWNTs dispersed in surfactant solutions are batch-dependent, as evidenced by luminescence and Raman spectroscopies, but are identical for metallic and semiconducting SWNTs within a batch. We thus find that small diameter SWNTs disperse at higher concentration in aqueous surfactants and dissolve at higher concentration in oleum than do large-diameter SWNTs. These results highlight the importance of controlling SWNT synthesis methods in order to optimize processes dependent on solubility, including macroscopic processing such as fiber spinning, material reinforcement, and films production, as well as for fundamental research in type selective chemistry, optoelectronics, and nanophotonics.

We have profiled promoter DNA methylation alterations in 272 glioblastoma tumors in the context of The Cancer Genome Atlas (TCGA). We found that a distinct subset of samples displays concerted hypermethylation at a large number of loci, indicating the existence of a glioma-CpG island methylator phenotype (G-CIMP). We validated G-CIMP in a set of non-TCGA glioblastomas and low-grade gliomas. G-CIMP tumors belong to the proneural subgroup, are more prevalent among lower-grade gliomas, display distinct copy-number alterations, and are tightly associated with IDH1 somatic mutations. Patients with G-CIMP tumors are younger at the time of diagnosis and experience significantly improved outcome. These findings identify G-CIMP as a distinct subset of human gliomas on molecular and clinical grounds., ((c) 2010 Elsevier Inc. All rights reserved.)

Hemangiomas of the heart are extremely rare. The prognosis is quite variable, because this benign tumor may grow, involute, or stop growing; therefore, resection is usually the treatment of choice. In patients with tumors of the left atrium, percutaneous balloon mitral valvulotomy is generally contraindicated. Yet for patients with moderate-to-severe mitral valve stenosis, balloon valvulotomy is an established therapy. Herein, we present the case of a 73-year-old woman who was referred to our department in 1995 with severe mitral valve stenosis. Echocardiography showed a valve orifice area of 0.9 cm2, according to Gorlin's formula, and a mean pressure gradient of 11 mmHg. Surgical therapy was declined by the patient. There were no signs of coronary artery disease. The injection of contrast medium into the left coronary artery showed a hemangioma at the posterior wall of the left atrium. Magnetic resonance imaging and transesophageal echocardiography confirmed the diagnosis. Despite the increased risk posed by the hemangioma, we performed successful percutaneous balloon mitral valvulotomy with an Inoue balloon. We saw the patient in 2001, and again in 2008 when she was 86 years of age. She was in excellent condition, with no signs of relevant dyspnea. Magnetic resonance imaging showed the size of the hemangioma to be stable. By use of echocardiography, we were able to confirm a good long-term result of the balloon valvulotomy. In this patient, a nonsurgical approach was adequate because of the lack of growth of the hemangioma in the left atrium.

Nanocomposites of TiO2 and multi-walled carbon nanotubes (MWNTs) were produced by the addition of different concentrations of MWNTs to a TiO2 sol matrix. Conductive coatings were prepared by spin coating the nanocomposite sols on glass substrates and sintering the samples at 300 degrees C for 15 min. No crystalline phase of TiO2 was formed at this temperature. The sheet resistance of the coatings was decreased from some hundreds of Momega/sq to just a few komega/sq by the addition of MWNTs to the TiO2 matrix. Moreover, sintering of the coatings in a reducing atmosphere has lead to a lower sheet resistance than that presented by coatings sintered in air. The lowest resistivity of 2.0 x 10(-1) omega x cm was obtained by coatings prepared with 5.0 mg/ml MWNTs in the composite sol. The optical, structural and electrical properties of the coatings were correlated and demonstrated.

A novel strategy is proposed for the topologically controlled synthesis of extended graphenic sheets by additively reacting carbon into a pre-existing graphene sheet which is on top of a templating substrate. This concept is implemented and demonstrated using chemical vapor deposition (CVD). Novel morphological features observed in this study suggest unusual aspects of the CVD growth process. CVD results demonstrate the basic soundness of the synthesis strategy but highlight the sensitivity of the process to certain types of disruption and the need for alternative forms of embodiment.

We show that, when subjected to microwave fields, surfactant-stabilized single-walled carbon nanotubes (SWNTs) develop polarization potentials at their extremities that readily drive electrochemical reactions. In the presence of transition metal salts with high oxidation potential (e.g., FeCl3), SWNTs drive reductive condensation to metallic nanoparticles with essentially diffusion-limited kinetics in a laboratory microwave reactor. Using HAuCl4, metallic particles and sheaths deposit regioselectively at the SWNT tips, yielding novel SWNT-metal composite nanostructures. This process is shown to activate exclusively metallic SWNTs; a degree of diameter selectivity is observed using acceptors with different oxidation potentials. The reaction mechanism is shown to involve Fowler-Nordheim field emission in solution, where electric fields concentrate at the SWNT tips (attaining approximately 10(9) V/m) due to the SWNT high aspect ratio (approximately 1000) and gradient compression in the insulating surfactant monolayer. Nanotube antenna chemistry is remarkably simple and should be useful in SWNT separation and fractionation processes, while the unusual nanostructures produced could impact nanomedicine, energy harvesting, and synthetic applications.

Ultraviolet (UV) irradiation of single wall carbon nanotubes (SWCNTs) individually dispersed in surfactants leads to diameter and type-selective photohydroxylation of the nanotubes. Photohydroxylation of first semiconductor and then small diameter metallic SWCNTs was confirmed after 254 nm UV irradiation in acidic, neutral, and basic aqueous solutions at ambient and elevated temperatures. The increased oxygen content of the SWCNTs after UV irradiation, as detected by X-ray photoelectron spectroscopy, suggests that SWCNTs were hydroxylated by reaction with water. Attenuated total reflectance Fourier transform infrared analysis provides evidence of hydroxyl functional groups on their surface. This photochemical reaction is impeded by molecular oxygen and appears to involve a reactive intermediate generated in the vicinity of semiconducting SWCNTs. This represents a noncontaminating selective reaction in the liquid phase that uses an intrinsic property of the tubes.

Background and Objective: Persisting disabling symptoms despite optimal medical treatment in patients with hypertrophic cardiomyopathy and significant outflow tract obstruction prompt surgical or interventional therapy targeted at relief of obstruction. While surgical treatment was introduced more than 40 years ago, there are only a few data on the long-term results of percutaneous septal ablation. This study gives the results of a large number of patients with hypertrophic obstructive cardiomyopathy (HOCM) who underwent septal ablation in our institution., Patients and Methods: 347 patients (156 females, 191 males, 54 +/- 15 years) in NYHA functional class III or IV, or in class II but with evidence of more severe limitation on exercise testing, underwent percutaneous transluminal septal myocardial ablation (PTSMA). Mortality and morbidity, as well as clinical and echocardiographic parameters were assessed during follow-up, either at our institution, or by the referring cardiologist., Results: During an average follow-up of 58 +/- 35 months the overall mortality was about 1,8 % per year, with a cardiovascular-related mortality of about 1 % per year. 8 % of patients needed a second procedure. A significant and sustained improvement of symptoms (89 % patients were in NYHA class I or II a follow-up) and obstruction were demonstrated (74 % of patients were free from obstruction at rest, 60 % did not exhibit provokable gradients). Supraventricular arrhythmias, especially atrial fibrillation, were observed in 12 % of patients., Conclusion: Percutaneous septal ablation provides significant and sustained beneficial effects on symptoms and echocardiographic variables, without evidence of an excess mortality. But independently of the clinical success of the procedure persistence of the underlying structural heart disease should be kept in mind. Periodic re-evaluation is mandatory to identify and treat high-risk patients.

We present a robust method for synthesis of aligned, single-walled carbon nanotube (CNT) "flying carpets" from nanostructured alumina flakes. Roll-to-roll e-beam deposition is utilized to produce the flakes, and hot filament chemical vapor deposition is utilized to grow dense, aligned carbon nanotubes from the flakes with remarkably high CNT yields. The flakes are captured inside a mesh cage and freely suspended in the gas flow during growth. Optical characterization indicates the presence of high quality, small diameter single-walled carbon nanotubes.

We theoretically investigate the separation of individualized metallic and semiconducting single-wall carbon nanotubes (SWNTs) in a dielectrophoretic (DEP) flow device. The SWNT motion is simulated by a Brownian dynamics (BD) algorithm, which includes the translational and rotational effects of hydrodynamic, Brownian, dielectrophoretic, and electrophoretic forces. The device geometry is chosen to be a coaxial cylinder because it yields effective flow throughput, the DEP and flow fields are orthogonal to each other, and all the fields can be described analytically everywhere. We construct a flow-DEP phase map showing different regimes, depending on the relative magnitudes of the forces in play. The BD code is combined with an optimization algorithm that searches for the conditions that maximize the separation performance. The optimization results show that a 99% sorting performance can be achieved with typical SWNT parameters by operating in a region of the phase map where the metallic SWNTs completely orient with the field, whereas the semiconducting SWNTs partially flow-align.

Aqueous surfactant suspensions of single walled carbon nanotubes (SWNTs) are very sensitive to environmental conditions. For example, the photoluminescence of semiconducting SWNTs varies significantly with concentration, pH, or salinity. In most cases, these factors restrict the range of applicability of SWNT suspensions. Here, we report a simple strategy to obtain stable and highly luminescent individualized SWNTs at pH values ranging from 1 to 11, as well as in highly saline buffers. This strategy relies on combining SWNTs previously suspended in sodium dodecylbenzene sulfonate (SDBS) with biocompatible poly(vinyl pyrrolidone) (PVP), which can be polymerized in situ to entrap the SWNT-SDBS micelles. We present a model that accounts for the photoluminescence stability of these suspensions based on PVP morphological changes at different pH values. Moreover, we demonstrate the effectiveness of these highly stable suspensions by imaging individual luminescent SWNTs on the surface of live human embryonic kidney cells (HEK cells).

Background and Objective: Echocardiographic tissue Doppler imaging (TDI) has been proposed for differentiating between constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM). The aim of this retrospective study was to analyse TDI in patients with severe diastolic dysfunction associated with proven constrictive pericarditis or restrictive cardiomyopathy., Patients and Methods: The cohort included 34 consecutive patients (24 men. 10 women; mean age 58 12 years), 20 of whom had proven CP (pericardectomy) and 14 had RCM due to amyloidosis (proven by biopsy). Tissue Doppler Imaging was performed online by pulsed-wave TDI at the lateral and septal mitral annulus in the four-chamber view. Filling pressures were measured invasively., Results: 20 of the 34 patients (60%) were in NYHA class III. 19 of the 34 patients were in sinus rhythm (56 %) and 15 had atrial fibrillation. Left ventricular systolic function was normal in all patients with CP. Eight patients with RCM had normal, 3 patients near normal and 3 patients slightly impaired left ventricular contractile function (EF 50-55% and EF 40%, respectively). Respiratory variation of the transmitral inflow was increased in 10 of 12 patients with CP and sinus rhythm. TDI of the early diastolic velocity across the mitral annulus E} was significantly higher in patients with CP than in those with RCM at the septal and at the lateral mitral annulus (13.8 4.2 cm/s vs. 4.0 1.2 cm/s; p < 0.01 and 11.4 3.4 cm/s vs. 4.4 1.7 cm/s; p < 0.01, respectively). A cut-off value 8 cm/s for the diagnosis of RCM showed a sensitivity of 100% and a specificity of 90% (septal) and 80% (lateral), respectively. The E/E}ratio also was significantly different between both groups (septal: 11.2 8.8 vs. 25.1 8.7; p < 0.01)., Conclusion: TDI of the early diastolic velocity of the mitral annulus E} makes it possible to differentiate between constrictive pericarditis and restrictive cardiomyopathy and should be part of the echocardiographic work-up in clinical routine.

Background: Single-walled carbon nanotubes (SWNTs) have remarkable physicochemical properties that may have several medical applications. The authors have discovered a novel property of SWNTs-heat release in a radiofrequency (RF) field-that they hypothesized may be used to produce thermal cytotoxicity in malignant cells., Methods: Functionalized, water-soluble SWNTs were exposed to a noninvasive, 13.56-megahertz RF field, and heating characteristics were measured with infrared thermography. Three human cancer cell lines were incubated with various concentrations of SWNTs and then treated in the RF field. Cytotoxicity was measured by fluorescence-activated cell sorting. Hepatic VX2 tumors in rabbits were injected with SWNTs or with control solutions and were treated in the RF field. Tumors were harvested 48 hours later to assess viability., Results: The RF field induced efficient heating of aqueous suspensions of SWNTs. This phenomenon was used to produce a noninvasive, selective, and SWNT concentration-dependent thermal destruction in vitro of human cancer cells that contained internalized SWNTs. Direct intratumoral injection of SWNTs in vivo followed by immediate RF field treatment was tolerated well by rabbits bearing hepatic VX2 tumors. At 48 hours, all SWNT-treated tumors demonstrated complete necrosis, whereas control tumors that were treated with RF without SWNTs remained completely viable. Tumors that were injected with SWNTs but were not treated with RF also were viable., Conclusions: The current results suggested that SWNTs targeted to cancer cells may allow noninvasive RF field treatments to produce lethal thermal injury to the malignant cells. Now, the authors are developing SWNTs coupled with cancer cell-targeting agents to enhance SWNT uptake by cancer cells while limiting uptake by normal cells., (2007 American Cancer Society)

Aim: The aim of this study was to analyze hemodynamic and clinical outcome in a cohort of 312 patients who were followed up over a period of 12 months after alcohol septal ablation (PTSMA) for symptomatic hypertrophic obstructive cardiomyopathy (HOCM)., Methods and Results: PTSMA was intended in 337 patients with HOCM (mean age: 54+/-15 years), with 312 procedures completed by injection of 2.8+/-1.2 ml of alcohol. In 25 patients (8%) the intervention was aborted, mostly because of contrast echocardiographic findings. In the 312 patients who received alcohol, permanent pacing was necessary in 22 cases (7%); and in-hospital mortality was 1.3% (four patients). During follow-up, contact to six patients (2%) was lost, and three additional patients (1%) died. The 299 patients who either underwent non-invasive reassessment in our institution or transmitted followup data from their local physician formed the study population. Improvement in symptoms was reported by 272 patients (91%). Mean NYHA functional class was reduced from 2.9+/-0.4 to 1.5+/-0.7 (p<0.0001) along with a gradient reduction (echo-Doppler) from 59+/-32 to 8+/-15 mmHg at rest, and from 120+/-42 to 28+/-32 mmHg with provocation (p<0.0001 each). Exercise capacity improved from 94+/-51 to 119+/-40 watts (p=0.001), and peak oxygen consumption from 18+/-4 to 21+/-6 ml/ kg/min (p=0.01). Younger age and higher outflow gradients at baseline and immediately after intervention were associated with a less favorable hemodynamic outcome. The degree of limitation of exercise capacity at baseline was the only predictor of symptomatic improvement., Conclusions: Catheter-based septal ablation is an effective non-surgical technique for reducing symptoms and outflow gradients in HOCM. In contrast to a previous study, in this cohort of 312 patients there was no association between post-interventional enzyme release and hemodynamic success. Younger patients with high baseline gradients, however, tended to have a less favorable hemodynamic outcome with higher residual gradients.

Aim: To provide tools for predicting the course of AV conduction disturbances after ethanol-induced septal ablation (PTSMA) for hypertrophic obstructive cardiomyopathy (HOCM)., Methods and Results: Based on a scoring system developed 1996-1998 and including parameters from baseline ECG, heart rate profile, severity of outflow obstruction (LVOTO), peri-interventional enzyme kinetics, and peri-interventional conduction problems, the risk of permanent AV block following PTSMA was assessed in 155 consecutive HOCM patients (pts.; mean age: 53+/-13 years) between 1999 and 2004. During PTSMA with 2.1+/-0.5 ml of ethanol, transient complete AV block occurred in 71 pts. (46%). Pts. were grouped into a low, intermediate, and high risk group for permanent conduction damage, and treated accordingly (early discharge from monitoring, prolonged monitoring, early DDD-PM implantation). Permanent pacing was necessary in 11 cases (7%), 0/116 of these (0%) in the low, 4/31 (13%) in the intermediate, and 7/8 (87%) in the high-risk group. While a new right bundle branch block was the most frequent ECG finding after PTSMA, a left bundle branch block at baseline was associated with 4 of the 11 DDD-PM implantations (p<0.0001). In-hospital mortality was 0%, short-term (3-months) follow up was complete. During follow-up, AV conduction recovered in 4 pts. (46%) with a DDD-PM. New onset AV blocks did not occur. Significant improvement of symptoms was reported by 141 pts. (91%)., Conclusions: Catheter-based septal ablation is an effective non-surgical technique for reducing symptoms and outflow gradients in HOCM. The proposed scoring system appears to reliably discriminate pts. with a high risk for permanent PM dependency from those with stable AV conduction after PTSMA. Pts. with left bundle branch block at baseline should undergo DDD-PM implantation prior to ablation.

With the desire to mass produce any specific n,m type of single wall carbon nanotube (SWNT) from a small sample of the same material, we disclose here the preliminary work directed toward that goal. The ultimate protocol would involve taking a single n,m-type nanotube sample, cutting the nanotubes in that sample into many short nanotubes, using each of those short nanotubes as a template for growing much longer nanotubes of the same type, and then repeating the process. The result would be an amplification of the original tube type: a parent SWNT serving as the prolific progenitor of future identical SWNT types. As a proof-of-concept, we use here a short SWNT seed as a template for vapor liquid solid (VLS) amplification growth of an individual long SWNT. The original short SWNT seed was a polymer-wrapped SWNT, end-carboxylated, and further tethered with Fe salts at its ends. The Fe salts were to act as the growth catalysts upon subsequent reductive activation. Deposition of the short SWNT-Fe tipped species upon an oxide surface was followed by heating in air to consume the polymer wrappers, then reducing the Fe salts to Fe(0) under a H2-rich atmosphere. During this heating, the Fe(0) can etch back into the short SWNT so that the short SWNT acts as a template for new growth to a long SWNT that occurs upon introduction of C2H4 as a carbon source. Analysis indicated that the templated VLS-grown long SWNT had the same diameter and surface orientation as the original short SWNT seed, although amplifying the original n,m type remains to be proven. This study could pave the way for an amplified growth process of SWNTs en route to any n,m tube type synthesis from a starting sample of pure nanotubes.

Individualized, chemically pristine single-walled carbon nanotubes have been intravenously administered to rabbits and monitored through their characteristic near-infrared fluorescence. Spectra indicated that blood proteins displaced the nanotube coating of synthetic surfactant molecules within seconds. The nanotube concentration in the blood serum decreased exponentially with a half-life of 1.0 +/- 0.1 h. No adverse effects from low-level nanotube exposure could be detected from behavior or pathological examination. At 24 h after i.v. administration, significant concentrations of nanotubes were found only in the liver. These results demonstrate that debundled single-walled carbon nanotubes are high-contrast near-infrared fluorophores that can be sensitively and selectively tracked in mammalian tissues using optical methods. In addition, the absence of acute toxicity and promising circulation persistence suggest the potential of carbon nanotubes in future pharmaceutical applications.

Hypercholesterolemia impairs endothelial function and subsequently decreases coronary vasodilatatory capacity. We examined the quantitative effects of one single LDL apheresis on vasodilatatory capacity. Using N-13 ammonia as a tracer for dynamic quantitative positron emission tomography (PET), mean myocardial perfusion measurements were carried out before and 20 h later after LDL apheresis, both under resting conditions and after pharmacological vasodilatation with dipyridamole. LDL apheresis was carried out using the heparin induced extracorporeal LDL precipitation (H.E.L.P.) procedure. We examined 47 patients (12 women and 35 men), with angiographically-proven coronary artery disease. All of them suffered from hypercholesterolemia. Of the patients, 35 received a chronic weekly H.E.L.P. procedure (group A), while H.E.L.P. procedure treatment was started for the first time in 12 patients, who were subsequently enrolled in a chronic apheresis program (group B). H.E.L.P. apheresis was combined with cholesterol lowering drugs in all patients. Both groups underwent positron emission tomography twice (prior to LDL apheresis and 20 h later). In group A, LDL cholesterol levels decreased from 175 +/- 50 mg/dL to 60 +/- 21 mg/dL immediately after H.E.L.P. (77 +/- 25 mg/dL before the second PET). Corresponding values for fibrinogen levels were 287 +/- 75 mg/dL to 102 +/- 29 mg/dL (155 +/- 52 mg/dL), minimal coronary resistance dropped from 0.56 +/- 0.20 to 0.44 +/- 0.17 mm Hg x 100 g x min/mL (P < 0.0001). Plasma viscosity decreased by 7.8%. In group B, LDL cholesterol decreased from 187 +/- 45 mg/dL to 75 +/- 27 mg/dL (85 +/- 29 mg/dL) and fibrinogen from 348 +/- 65 mg/dL to 126 +/- 38 mg/dL (168 +/- 45 mg/dL). Minimal coronary resistance was reduced from 0.61 +/- 0.23 to 0.53 +/- 0.19 mm Hg x 100 g x min/mL (P < 0.01). Plasma viscosity was observed to decrease by 7.6%. The strong LDL drop in patients under chronic H.E.L.P. treatment has a significant impact on coronary vasodilatatory capacity within 20 h leading to an improved overall cardiac perfusion. Nearly the same effect can be seen in patients after their first H.E.L.P. treatment.

A transfer of a VA-SWNT film onto a conductive surface has been achieved using a novel "flip-over" technique. The top surface of a VA-SWNT film was covered by entangled bundles in an as-grown sample. When a VA-SWNT film was flipped over, an optically flat surface consisting of the tips of very well aligned, clean bundles from the bottom of the film are exposed while the top of the film is well contacted to the substrate. Thus, we expect this technique to provide us with means to prepare carbon nanotube electrodes for device applications such as super capacitors, thermo-electric devices, fuel cells, and field emission filaments.

We report a study on Dielectrophoresis Field Flow Fractionation of Single-Wall Carbon Nanotubes (SWNTs). SWNTs, individually suspended in 1% SDBS solution, were separated by type when they passed a dielectrophoresis field flow fractionation device where 1 MHz AC voltage was supplied and the field strength was well below 1 V per mum. Furthermore, we uniquely observed enrichment of semiconductive SWNTs based on their band gap. In addition to Raman spectrum, UV-vis absorption and NIR fluorescence spectra were used for solution samples for characterization.

We present the first quantitative assessment of the maximum amount of nanotubes that can exist in the isotropic phase () of single-walled carbon nanotubes (SWNTs) in Brønsted-Lowry acids. We employ a centrifugation technique in conjunction with UV-vis-nIR spectroscopy to quantify , which is also the critical concentration of the isotropic-nematic transition of SWNTs in strong acids. Centrifugation of biphasic dispersions of SWNTs, that is, acid dispersions consisting of an isotropic phase in equilibrium with an ordered nematic liquid crystalline phase, results in a clear phase separation, where the isotropic phase is supernatant. Dilution of the isotropic phase with a known amount of acid followed by UV-vis-nIR absorbance measurements yields , that is, the maximum concentration of SWNTs that can exist in the isotropic phase in a given acid for a given SWNTs' length distribution. At low SWNT concentration (below 200 ppm) in superacids, light absorbance in the range from 400 to 1400 nm scales linearly with concentration. This Beer's law behavior yields calibration curves for measuring SWNTs' concentration in acids. We find that the critical concentration of the isotropic-nematic transition increases with acid strength in accordance with the previously proposed sidewall protonation mechanism for dispersing SWNTs in acids.

This article reviews aetiology, natural history, and current treatment options in hypertrophic cardiomyopathy with a special focus on percutaneous septal ablation, which has evolved as an alternative to myectomy in patients with outflow obstruction and symptoms refractory to medical treatment. Literature data and the own series of 382 interventions (in-hospital mortality and pacemaker implantation rates: 1.2% and 7%, respectively) are discussed. Overall satisfactory clinical results were seen in about 90% of the patients treated with septal ablation.

Aims: To analyze the impact of intra-procedural echocardiographic imaging on the interventional strategy in ethanol-induced septal ablation (PTSMA) for symptomatic hypertrophic obstructive cardiomyopathy (HOCM), based on a single-center experience of 7 years., Methods and Results: PTSMA was intended for refractory symptoms in 337 patients (pts.) with HOCM (mean age: 54 +/- 15 years), with 312 procedures completed by injection of 2.8 +/- 1.2 ml ethanol. In 25 pts. (8%) the intervention was aborted without ethanol injection, mostly because of echocardiographic findings (n = 18/6%). An echocardiography-driven target vessel change was necessary in 33 pts. (11%). In the 312 pts. who received ethanol, permanent pacing was necessary in 22 cases (7%). In-hospital mortality was 1.3% (4 pts.). After 3 months, mean NYHA functional class was reduced from 2.9 +/- 0.5 to 1.5 +/- 0.6 (p < 0.0001) along with a gradient reduction from 60 +/- 33 to 13 +/- 18 mmHg at rest, and from 120 +/- 43 to 38 +/- 35 mmHg with provocation (p < 0.0001 each). Exercise capacity improved from 94 +/- 51 to 115 +/- 43 W, peak oxygen consumption from 18 +/- 4 to 21 +/- 6 ml/kg/min (p < 0.01 each). There was no significant difference regarding residual gradients in pts. with different levels of immediate gradient reduction during probatory balloon occlusion., Conclusions: Catheter-based septal ablation is an effective non-surgical technique for reducing symptoms and outflow gradients in HOCM. Intra-procedural echocardiographic guidance has a cumulative impact on the interventional strategy in about 15-20%, and clearly identifies pts. who should not receive ethanol but undergo a surgical myectomy.

Background and Aim of the Study: Patients with restenosis after open or closed surgical commissurotomy (SC) often demonstrate more severe valve degeneration than patients without prior surgery. This may affect the result of balloon mitral valvotomy (BMV) in this patient group., Methods: The immediate- and long-term results (maximum 106 months; mean 26 months) of BMV with the Inoue balloon in patients with prior SC were compared with findings in patients without prior surgery. Between February 1989 and July 2001, a total of 1,156 BMV interventions was performed, of which 127 were conducted in patients (106 women, 21 men; mean age 56 +/- 12 years) with prior SC., Results: After BMV, the mitral valve area (MVA) increased from 1.0 +/- 0.2 cm2 to 1.6 +/- 0.4 cm2 after SC compared with 1.0 +/- 0.3 cm2 to 1.8 +/- 0.4 cm2 without SC. After three months, the average MVA was 1.7 +/- 0.3 cm2 in both patient groups. The mean NYHA class improved from 2.8 to 2.0 (after SC) versus 2.7 to 1.8 (no SC) three months after BMV. The main complications were cardiac tamponade in three patients (2.4 %), and more than moderate mitral regurgitation (grade 2+) in six (4.7 %) compared to 5.8% in no-SC patients., Conclusion: In view of the satisfactory clinical and hemodynamic results, BMV with the Inoue balloon can be considered the treatment of choice for mitral valve restenosis after SC in selected patients.

Background and Objective: Percutaneous mitral valvotomy (MVT) with the Inoue balloon is the most frequently performed therapeutic alternative to surgical commissurotomy in patients with symptomatic mitral valve stenosis. Few data are available on the results of repeat MVT., Patients and Methods: We compared the immediate and 3-month results of all patients who had a repeat MVT (n = 39) with those who had a primary intervention (n = 1,117) in our institution between February 1989 and January 2001. Mean age of the 31 women and 8 men with repeat MVT was 53 +/- 14 years at the first and 57 +/- 14 years at the second intervention performed 3 - 10 years later., Results: Following primary intervention the invasively assessed mitral valve are (MVA) had increased from an average of 1.0 +/- 0.2 cm(2) to 1.7 +/- 0.4 cm(2). Echocardiography three months after the intervention revealed a MVA of 1.7 +/- 0.3 cm(2). Repeat MVT resulted in an immediate increase of MVA from 1.0 +/- 0.2 cm(2) to 1.6 +/- 0.4 cm(2), after 3 months the average MVA was 1.6 +/- 0.3 cm(2). According to the NYHA classification clinical symptoms had improved on average from 2.6 to 1.6 three months after primay intervention and from 2.8 to 2.1 three months following the repeat procedure. The incidence of significant procedure-related complications was less than 3 % for both primary and repeat MVT., Conclusion: The clinical and hemodynamic results demonstrated in our patients suggests repeat MVT as the treatment option of choice in mitral restenosis after previous balloon intervention, if mitral valve morphology is still suitable.

In children with familial hypercholesterolemia, coronary heart disease requires both medical theraphy and LDL apheresis. We report a case of verified occlusion of the anterior descending branch of the left coronary artery in a 10-year-old patient. The pathological findings revealed by ergometry established the diagnosis. The goal was to achieve the greatest possible reduction of lipid parameters and fibrinogen by lowering plasma viscosity employing LDL apheresis. It is astonishing that this treatment is also well tolerated by children. The basic vascular approaches suffice and shunt operations are not absolutely necessary. The efficacy of this method became vividly apparent by the changes in the skin lesions. Additional angiographic follow-up and further clinical course wil provide information on the usefulness of this treatment strategy with maximum lipid theraphy and the expected improvement in prognosis.

The authors describe the case of a 76-year-old woman who presented with acute inferior myocardial infarction 8 years after prosthetic aortic valve replacement. Echocardiography and cardiac catheterization revealed a false aneurysm of the ascending aorta with fistulous communication to the right ventricle. The right coronary artery originated from the false aneurysm with no antegrade perfusion.

Background and Introduction: Damage to the AV conduction system is a frequent complication of percutaneous septal ablation (PTSMA) that needs early and reliable identification of those patients (pts.) at risk for complete heart block (CHB) and subsequent pacemaker implantation., Methods and Results: In the first 39 pts. who underwent PTSMA in 1996, AV conduction recovery needed up to 11 days. One pt. suffered from unexpected CHB after 9 days. Seven pts. who needed a DDD pacemaker (DDD-PM) were compared to those without conduction disturbances. A score was established which identified all DDD-PM candidates retrospectively if they presented with >12 score points. In the following 137 consecutive pts. treated in 1997 and 1998, this score was applied prospectively, and again correctly identified all candidates for a DDD-PM. In addition, a low risk group was identified with <8 score points. From 1999 on, the score was applied in routine clinical decision-making in 120 consecutive pts. with respect to DDD-PM implantation. All low risk pts. (<8 points) remained free from bradycardias, while 2/54 pts. (4%) of the intermediate risk group, and 20/23 pts. (87%) of the high risk group had to undergo DDD-PM implantation. Pts. with a first-degree AV block or those with a right bundle branch block at baseline had no excess risk, while 50% of the pts. with a left bundle branch block (LBBB) needed a DDD-PM., Conclusions: Based on pre-interventional data and careful monitoring of the first 48 hours after PTSMA, identification of pts. at risk for CHB and subsequent DDD-PM implantation seems to be possible. Pts. with a score <8 seem to be at low, those with >12 points at high risk. In the remaining cases watchful waiting with prolonged monitoring may allow AV conduction to recover, thus, reducing the number of unnecessary DDD-PM implantations. In cases with LBBB at baseline, however, implantation of a DDD-PM should be considered first-line therapy.

Due to endothelial dysfunction (ED), coronary vasodilation capacity is reduced in patients with hypercholesterolemia. Cholesterol lowering may largely restore endothelial function. Currently, it is supposed that the onset of this therapeutic effect takes weeks or even months. However, by means of LDL apheresis, a significant LDL reduction may be achieved within hours. Dynamic quantitative positron emission tomography (PET) performed before and after LDL apheresis showed that mean global myocardial perfusion can be measured at rest and after pharmacological vasodilation with dipyridamole using N13 ammonia as tracer.A total of 35 patients (11 women and 24 men) with documented coronary heart disease and hypercholesterolemia underwent PET immediately prior to LDL apheresis and 18-20 hours thereafter. In addition to the decrease in LDL cholesterol (from 175+/-50 to 77+/-25 mg/dl) and fibrinogen (from 287+/-75 to 155+/-52 mg/dl), a significant improvement of myocardial blood flow under dipyridamole (177+/-59 vs 217+/-82 ml/min 100 g, p<0.0001), of coronary flow reserve (2.10+/-0.82 vs 2.62+/-1.02, p<0.0001) and of minimal coronary resistance (0.56+/-0.20 vs 0.44+/-0.17 mmHg 100 g min/ml, p<0.0001) were achieved. Plasma viscosity decreased only by 7.8%. Within 20 hours after single LDL apheresis a 20% improvement of coronary vasodilation capacity was noninvasively demonstrated and quantified.

An acute Lyme carditis affects about 0.3-4% of patients with Lyme borreliosis. The acute period of the disease may be associated with critical atrioventricular conduction abnormalities (complete heart block), supraventricular and ventricular arrhythmias as well a left ventricular failure. Normally, Lyme carditis is completely reversible. Therefore the prognosis largely depends on the management of the acute complications and early antibiotic therapy. Even if the symptoms are spontaneously reversible, antibiotic therapy should be applied to prevent a chronic cardiomyopathy and other manifestations of Lyme borreliosis. We report on a 47-year old patient with acute ECG changes initially suggesting an acute coronary syndrome. However, case history and the erythema migrans indicated an acute Lyme carditis which was confirmed serologically and by myocardial biopsy later.