Dielectric wakefield acceleration of a relativistic electron beam in a slab-symmetric dielectric lined waveguide.

We report first evidence of wakefield acceleration of a relativistic electron beam in a dielectric-lined slab-symmetric structure. The high energy tail of a ∼60 MeV electron beam was accelerated by ∼150 keV in a 2 cm-long, slab-symmetric SiO2 waveguide, with the acceleration or deceleration clearly visible due to the use of a beam with a bifurcated longitudinal distribution that serves to approximate a driver-witness beam pair. This split-bunch distribution is verified by longitudinal reconstruction analysis of the emitted coherent transition radiation. The dielectric waveguide structure is further characterized by spectral analysis of the emitted coherent Cherenkov radiation at THz frequencies, from a single electron bunch, and from a relativistic bunch train with spacing selectively tuned to the second longitudinal mode (TM02). Start-to-end simulation results reproduce aspects of the electron beam bifurcation dynamics, emitted THz radiation properties, and the observation of acceleration in the dielectric-lined, slab-symmetric waveguide.

On the uncertainty estimation of electromagnetic field measurements using field sensors: a general approach.

One of the most common and popular practices on measuring the non-ionising electric and/or magnetic field strength employs field meters and the appropriate electric and/or magnetic field strength sensors. These measurements have to meet several requirements proposed by specific guidelines or standards. On the other hand, performing non-ionising exposure assessment using real measurement data can be a very difficult task due to instrumentation limits and uncertainties. In addition, each measuring technique, practice and recommendation has its own drawbacks. In this paper, a methodology for estimating the overall uncertainty for such measurements, including uncertainty estimation of spatial average values of electric or magnetic field strengths, is proposed. Estimating and reporting measurement uncertainty are of great importance, especially when the measured values are very close to the established limits of human exposure to non-ionising electromagnetic fields.

Electromagnetic exposure compliance estimation using narrowband directional measurements.

The increased number of everyday applications that rely on wireless communication has drawn an attention to several concerns on the adverse health effects that prolonged or even short time exposure might have on humans. International organisations and countries have adopted guides and legislation for the public safety. They include reference levels (RLs) regarding field strength electromagnetic quantities. To check for RLs compliance in an environment with multiple transmitters of various types, analytical simulation models may be implemented provided that all the necessary information are available. Since this is not generally the case in the most practical situations, on-site measurements have to be performed. The necessary equipment for measurements of this type usually includes broadband field metres suitable to measure the field strength over the whole bandwidth of the field sensor used. These types of measurements have several drawbacks; to begin with, given that RLs are frequency depended, compliance evaluation can be misleading since no information is available regarding the measured spectrum distribution. Furthermore, in a multi-transmitter environment there is no way of distinguishing the contribution of a specific source to the overall field measured. Of course, this problem can be resolved using narrowband directional receiver antennas, yet there is always the need for a priori knowledge of the polarisation of the incident electromagnetic wave. In this work, the use of measurement schemes of this type is addressed. A method independent to the polarisation of the incident wave is proposed and a way to evaluate a single source contribution to the total field in a multi-transmitter environment and the polarisation of the measured incident wave is presented.

Detection of cancerous endobronchial lesions by autofluorescence bronchoscopy combined with mutation analysis of p53.

Early lung cancer screening failed to reduce lung cancer mortality. New techniques such as autofluorescence bronchoscopy (AF) and the identification of specific genetic alteration might change future outcomes of lung cancer screening. It was the aim of our study to combine p53 analysis with white-light bronchoscopy (WL) or WL and AF to improve the diagnostic yield in a series of 36 patients with histologically proven lung cancer, pulmonary metastasis or suspected lung cancer. - Endobronchial sites were analysed by WL (n = 71), AF (Storz) (n = 34), histopathology (n = 71) and p53 mutations were examined by SSCP analysis on additional biopsies (n = 69). The overall frequency of cancerous lesions was 19, of which 14 were macroscopically visible lesions. The addition of p53 and autofluorescence improved the yield to 17 of 19 cases. In 7 preinvasive lesions (dysplasia/metaplasia) 4 were identified macroscopically and 5 of 7 lesions by all 3 methods. In the WL/p53 group the diagnostic yield was 7 of 9 cancerous lesions compared to 10 of 10 cancerous lesions in the AF group. It should be noted that all methods were associated with false positive results. However, the combination of conventional with autofluorescence bronchoscopy and mutation analysis is a promising approach which is applicable to clinical routine and may be further enhanced by the inclusion of a panel of markers of tumour progression.

Molecular oncology--perspectives in lung cancer.

Despite novel therapies in lung cancer treatment the 5-year survival rate still remains poor. Furthermore, screening concepts for early diagnosis, based on conventional sputum cytology and chest radiography, have so far not demonstrated an impact on decreasing lung-cancer mortality. More specific molecular markers allow new insights in the process of lung carcinogenesis. Furthermore they raise the hope that they provide new tools for early diagnosis and screening of high-risk individuals, determination of prognosis, and identification of innovative treatments. In this review, these perspectives of molecular targets in lung cancer will be discussed and summarised. Angiogenesis-stimulating factors (VEGF, FGF, MMP, etc.), parameters concerning tumour cell proliferation and apoptosis (EGFR, p53, K-ras, rb, bcl-2, etc.) are well known. Several of these genetic factors have already been investigated, but no single parameter has yet gained a sufficient selectivity regarding prognostic significance or therapeutic efficacy. New aspects in the complex tumour-stroma interaction and the interactive, cross-talking signal transduction pathways and recently developed functional genomic approaches, such as DNA microarrays and proteomics might lead to further progress in biological staging models and treatment concepts.

[High prevalence of osteoporosis in adult cystic fibrosis patients]. / Hohe Osteoporose-Prävalenz bei erwachsenen Patienten mit zystischer Fibrose.

BACKGROUND AND OBJECTIVE: In adult patients with cystic fibrosis bone metabolism may be altered by multiple mechanisms, such as abnormal calcium homeostasis, malnutrition, chronic inflammation or inactivity in the course of respiratory failure. In contrast to the high prevalence of osteoporosis in CF patients before lung transplantation, data from different CF collectives show great variation. It was the purpose of our cross-sectional study to determine changes in bone metabolism by measuring bone mineral density, and assessing calcium metabolism and clinical characteristics in adult patients (mean age 32 years) with cystic fibrosis. PATIENTS AND METHODS: Bone mineral density (quantitative digital radiography), parameters of calcium homeostasis and clinical characteristics were determined in 34 adult patients with cystic fibrosis. RESULTS: The mean age of the study population was 32 years (range 20 to 47; 21m: 13f). 13 patients had normal T-values (mean bone mineral density in young adults), whereas 11 patients (32 %) had osteopenia and 10 (29 %) had osteoporosis. Calcium homeostasis was abnormal in only one case. In contrast T-values were positively correlated with a low body mass index (p = 0.01) and a low one-second forced expiratory volume (FEV1) (p < 0.05). CONCLUSION: Decreased mineral bone density is a frequent complication in adult patients with cystic fibrosis, but does not occur inevitably even in long-standing disease (up to 47 years). In our cohort measurable alterations of calcium homeostasis could be avoided by consistent substitution policy. The main determinants of a low T-value were poor nutritional status, lowered serum calcium or phosphate concentrations and severely impaired lung function as indicator of the progression of the disease. Screening of adult patients with CF can be recommended especially in presence of malnutrition or poor lung function.

[Asthma attack out of control--what to do? Therapy of acute asthma exacerbation depends on severity]. / Asthmaanfall ausser Kontrolle--was tun? Therapie der akuten Asthmaexazerbation abhängig vom Schweregrad.

Treatment of acute asthma exacerbation is determined by the severity of the attack, making it necessary to grade the latter using objective parameters such as clinical symptoms, respiratory rate, heart rate, oxygen saturation and FEV1 or PEF. Severity grading is also essential for the further management--need for early hospitalization--in particular in the case of risk patients. Apart from the treatment of hypoxia, first-line treatment comprises bronchodilation with beta-2-agonists. Anti-inflammatory measures applying corticosteroids are indicated, in particular in moderate to severe exacerbation, while inhalative anticholinergics and theophyline are available in addition when primary treatment fails, and in the case of severe exacerbations.

Effects of ultrapure dialysis fluid on nutritional status and inflammatory parameters.

BACKGROUND: Malnutrition and chronic systemic inflammatory response syndrome not only coexist in uraemia, but may also have a bi-directional cause-and-effect relationship. To evaluate the role of dialysate-related cytokine induction in inflammatory response and nutritional status, we conducted a prospective comparison of two dialysis fluids differing in their microbiological quality. METHODS: Forty-eight early haemodialysis patients were assigned to either treatment with conventional (potentially microbiologically contaminated) or on-line produced ultrapure dialysis fluid. Study parameters were bacterial growth, markers of systemic inflammation (C-reactive protein (CRP) and interleukin 6), and parameters of nutritional status (estimated dry weight, upper mid-arm muscle circumference, serum albumin concentration, insulin-like growth factor 1, leptin, and protein catabolic rate). Patients were followed for 12 months. RESULTS: There were no statistically significant differences in demographic and treatment characteristics, degree of bacterial contamination of the dialysate, markers of systemic inflammation, or parameters of nutritional status among the two treatment groups at recruitment. Changing from conventional to ultrapure dialysis fluid reduced significantly the levels of IL-6 (19+/-3 pg/ml to 13+/-3 pg/ml) and CRP (1.0+/- 0.4 mg/dl to 0.5+/-0.2 mg/dl), and resulted in significant increases in estimated dry body weight, mid-arm muscle circumference, serum albumin concentration, levels of the humoral factors, and in protein catabolic rate after 12 months. Continuous use of conventional dialysis fluid (median 40-60 c.f.u./ml) was not associated with significant alterations in markers of inflammation (IL-6 21+/-4 pg/ml vs 24+/-6 pg/ml, CRP 0.9+/-0.3 mg/dl vs 1.1+/-0.4 mg/dl) or of nutritional status at any time of the study. All differences in systemic inflammation and nutritional parameters observed during the study period (from recruitment to month 12) were significant between the two patient groups. CONCLUSIONS: Cytokine induction by microbiologically contaminated dialysis fluid has a negative impact on nutritional parameters of early haemodialysis patients. The microbiological quality of the dialysis fluid represents an independent determinant of the nutritional status in addition to known factors, such as dose of dialysis and biocompatibility of the dialyser membrane. Ultrapure dialysis fluid adds to the cost of the dialytic treatment, but may improve the nutritional status in long-term haemodialysis patients.

Detection of K-ras and p53 mutations in bronchoscopically obtained malignant and non-malignant tissue from patients with non-small cell lung cancer.

Molecular screening may increase the likelihood to identify early malignant lesions in non-small cell lung cancer. However the presence of gene mutations in non-malignant bronchial tissue has remained controversial. The present study was carried out to investigate systematically the presence of mutations of the K-ras and p53 gene in bronchial biopsies taken during routine bronchoscopy of normal as well as tumour tissues from a series of 40 patients with histologically verified non-small cell lung cancer (NSCLC). K-ras mutations were analysed with specific detection oligonucleotides, p53 mutations were examined by SSCP analysis. In all biopsies the wildtype of both K-ras and p53 could be detected. The overall frequency of mutations was 14 (35%) with 2 K-ras mutations (5%) and 12 mutations of the p53 gene (30%). In 3 cases (1 ras mutation, 2 p53 mutations) the same mutation could be shown in the tumour biopsy and in the distant normal control. In another case only the normal appearing tissue had a mutation of the p53 gene. All other mutations could be detected in the tumour tissue only. Our data confirm that K-ras mutations and p53 can be detected not only in malignant but also in non-malignant bioptic samples from patients with NSCLC. The use of molecular screening for the early detection of lung cancer may be a promising new approach.

Molecular screening of patients with long standing extensive ulcerative colitis: detection of p53 and Ki-ras mutations by single strand conformation polymorphism analysis and differential hybridisation in colonic lavage fluid.

BACKGROUND: In patients with long standing ulcerative colitis at risk of developing malignancy, mutations of the p53 and Ki-ras gene were investigated in lavage solution obtained at surveillance colonoscopy. METHODS: DNA was isolated from 31 consecutive patients with total or subtotal ulcerative colitis and a disease duration of between seven and 26 years. Twenty seven control patients showed no macroscopic or microscopic inflammation on colonoscopy. Exons 5-8 of the p53 gene and exon 1 of the Ki-ras gene were amplified by polymerase chain reaction. Mutations of the p53 gene were detected by single strand conformation polymorphism analysis. Point mutations of the Ki-ras gene were hybridised on dot blots with oligonucleotides marked with digoxigenin. RESULTS: In all cases of ulcerative colitis and in all of the 27 control patients, wild type p53 and wild type Ki-ras could be detected. In four patients with ulcerative colitis, a mutation in exon 5 to 7 of the p53 gene was found, and two patients had a mutation of the Ki-ras gene (Gly to Asp-12, Gly to Val-12). None of these patients had dysplasia in serial biopsy specimens, and all but one had had the disease for more than 10 years. One control patient had a mutation. CONCLUSIONS: Mutations were more frequent in patients with long standing ulcerative colitis (19%) than in control patients (3%, p = 0.07). The technique may be useful for screening for early malignancy in ulcerative colitis.

[Pulmonary trichomoniasis: diagnosis based on identification of irritation in bronchoalveolar lavage]. / Pulmonale Trichomoniasis: Diagnose durch Erregernachweis in der bronchoalveolären Lavage.

Bronchopulmonary infections caused by trichomonads have been reported mainly in patients with pre-existing pulmonary or debilitating disease (e.g. bronchial carcinoma, lung abscess, bronchiectasis). Pulmonary trichomoniasis is most often due to infection with Trichomonas tenax, usually regarded as a harmless commensal of the human mouth, and may rarely be caused by other trichomonas species. A 45 year old female presented with a dry cough, exertional dyspnoea and malaise. These symptoms persisted for 6 months regardless of anti-inflammatory and anti-obstructive inhalative therapy. Sarcoidosis of the lungs, diagnosed 20 years prior, had been asymptomatic since and there was no coexistent disease. Laboratory data revealed increased ACE-levels (90 IE/ml) and lung function showed bronchial hyperreactivity on histamine challenge. No other abnormalities were found (chest x-ray, bronchoscopy, lung function test, blood count and serum calcium). The diagnosis was based on the cytological identification of numerous trophozoites of T. tenax in the bronchoalveolar lavage. Therapy with oral metronidazol for 40 days led to complete recovery from symptoms and normalisation of ACE serum levels. The patient has remained well for 12 months since. The pathogenicity of oral trichomonads in the non-immunocompromised host remains uncertain. Our patient had no known medical risk factors by comparison with published cases. The case illustrates the clinical relevance of pulmonary trichomoniasis in an otherwise healthy person.

Detection of Ki-ras mutations by PCR and differential hybridization and of p53 mutations by SSCP analysis in endoscopically obtained lavage solution from patients with long-standing ulcerative colitis.

OBJECTIVES: The goal of this study was the early detection of malignant transformation in patients with long-standing ulcerative colitis; therefore, mutations of the Ki-ras and p53 gene were analyzed in lavage solution and biopsies obtained at surveillance colonoscopy. METHODS: DNA was isolated from 14 patients (nine female, five male) with a history of pancolitis for more than 10 yr. Exon 1 of the Ki-ras gene and exons 5-8 of the p53 gene were amplified via polymerase chain reaction. Mutations of the p53 gene were detected via single-strand conformation polymorphism analysis; point mutations of the Ki-ras gene were hybridized on dot blots with oligonucleotides marked with digoxigenin. RESULTS: Wild-type Ki-ras and wild-type p53 were detected in all cases of ulcerative colitis and in four of seven control patients. In two ulcerative colitis patients, a mutation was found in the Ki-ras gene (Gly --> Asp 12 and Gly --> Val 12), and in one patient, a mutation in exon 5 of the p53 gene. Mutations were found only in the lavage fluid, whereas random biopsies were negative. CONCLUSIONS: From colonic lavage fluid, it is possible to extract DNA of sufficient quantity and quality for polymerase chain reaction-based amplification and subsequent analysis via single-strand conformation polymorphism or hybridization. Mutations were found in three of 14 patients with long-standing ulcerative colitis but were not found in controls. The method may be useful for the screening of such patients.