Transmission-mode MALDI-2 mass spectrometry imaging of cells and tissues at subcellular resolution.

Matrix-assisted laser desorption-ionization mass spectrometry imaging in transmission-mode geometry (t-MALDI-MSI) can provide molecular information with a pixel size of 1 µm and smaller, which makes this label-free method highly interesting for characterizing the chemical composition of tissues and cells on a (sub)cellular level. However, a major hindrance for wider use of the technology is the reduced ion abundance at small pixel sizes. Here we mitigate this problem by use of laser-induced post-ionization (MALDI-2) and by adapting a t-MALDI-2 ion source to an Orbitrap mass analyzer. We demonstrate the crucial sensitivity and accuracy boosts that are achieved with this combination by visualizing the distribution of numerous phospho- and glycolipids in mouse cerebellum and kidney slices, and in cultured Vero B4 cells. With brain tissue, a pixel size of 600 nm was achieved. Our method could constitute a valuable new tool for research in cell biology and biomedicine.

[Assistive Services in the Workplace of People with Hearing Impairment in the State of North Rhine-Westphalia]. / Inanspruchnahme begleitender Hilfen im Arbeitsleben von hörgeschädigten Arbeitnehmerinnen und Arbeitnehmern in Nordrhein-Westfalen.

AIM OF THE STUDY: Assistive services in the workplace are an important aspect of the participation of people with hearing impairment in working life. This article presents the results of the GINKO study and an survey conducted by the University of Cologne on behalf of the MAIS in order to provide a comprehensive examination of the employment situation of hearing impaired people in North Rhine-Westphalia. The GINKO study examines the impact of laws on the integration of hard-of-hearing and deaf people as well as people who have become deaf as adults, focusing on communication and organizations; this project was funded by the German Federal Ministry for Labour and Social Affairs (BMAS). METHOD: In the GINKO study, conducted in cooperation with the German Association of the Hard of Hearing and the German Association of the Deaf, a standardised questionnaire with questions about the workplace was administered to employed people with hearing impairments. The questionnaire was administered on paper and was also available online accompanied by sign language videos. The University of Cologne study in North Rhine-Westphalia examined the service situation of hard-of-hearing, deaf and deaf-blind people through face-to-face interviews and government statistics. RESULTS: The results of the nationwide GINKO study show that hearing-impaired people in North Rhine-Westphalia draw on assistive services in employment more often than hearing-impaired people in the rest of Germany. The study found statistically significant differences in the categories of "maintenance and development of professional knowledge and skills" and "psychosocial support in conflict situations resulting from disability". CONCLUSION: One reason for the more positive evaluations of the participants in North Rhine-Westphalia as compared to other regions in Germany could be the particular network of support services in that state. However, the overall positive results from North Rhine-Westphalia should not obscure the fact that a majority of participants in many areas of North Rhine-Westphalia reported much less positive evaluations. They reported that they did not (yet) have an accessible workplace and that assistive services are not available to all hearing impaired workers.

[The UN-Convention on the Rights of People with Disabilities and the transition from school to vocational training and career in Germany: public data sources under close scrutiny]. / Die UN-Behindertenrechtskonvention und der Übergang Schule-Ausbildung-Beruf in Deutschland: Öffentliche Datenquellen auf dem Prüfstand.

This paper analyzes public data sources and their requirements for the transition from school to vocational training and career of people with disabilities in the context of Article 31 of the UN-Convention on Rights of People with Disabilities. Different focuses of the public data sources within the involved systems and challenges in data analysis will be presented. These manifest themselves as cross-system interface problems when it comes to the identification and whereabouts of young people with disabilities at the transition from school to vocational training and employment. With these challenges public data sources on the transition from school to vocational training and employment are especially under scrutiny when it comes to developing and implementing policies in respect to the Convention on Rights for People with disabilities and the provision of adequate planning data.

[Rehabilitation counselors' vocational fields of activity: empirical findings of an exploratory study in Germany]. / Tätigkeitsbereiche von Beratungsfachkräften in der beruflichen Rehabilitation: Empirische Befunde einer explorativen Befragung in Deutschland.

BACKGROUND AND OBJECTIVE: In the light of far-reaching demographic and sociopolitical changes, the demand for rehabilitation counseling experts increases. Internationally scientific research has long recognised the importance of professional support for successful vocational rehabilitation of people with illnesses and disabilities. In Germany, however, there has been a lack of systematic research in this field. The present exploratory study aims to fill this gap by investigating the status quo of rehabilitation counselors' vocational fields of activity in Germany. METHOD: The study was conducted anonymously as an online-survey. An international questionnaire which covers a wide range of tasks that can play a role in the day-to-day work of rehabilitation counseling experts was used. Within the project it was translated into German and adapted to the German rehabilitation system. 217 rehabilitation counselors completed the survey. Socio-demographic information and information concerning the participant's working biography were evaluated descriptively. To analyze the questionnaire data, principal component analysis was undertaken. RESULTS: The majority of respondents indicated to be performing tasks from different fields of activity in their daily routine. The essential and main field of activity though appeared to be the individual work with the client. Managerial tasks on an organizational level turned out to be less important. Furthermore, it became clear that the terms the respondents used to name their qualification and their current job title varied in a confusing way. This implicates that it was not always possible to infer from the job title of a person to their actual vocational tasks. Moreover, the participants expressed that they see a need for action concerning their vocational training as well as their professional tasks. DISCUSSION: German rehabilitation counseling experts can be characterized as "generalists" who cover different fields of activity in their daily routine. Their main activity is the individual work with the client while managerial tasks play a lesser role yet. A further differentiation of the vocational tasks indicating a higher degree of specialization as it can be found in related American or Australian studies does not emerge. The take-over of managerial tasks on an organizational level is not necessarily associated with the use of the term "management" in a person's job title. These results can be explained partly by the relatively new sociopolitical changes in Germany. These changes include the introduction of a regulation in 2004 (§ 84 Social Code Book), which obliges employers to prevent and manage disability at the company level. Still different studies show various problems concerning the comprehensive implementation of this regulation. The participants see urgent needs for action concerning the clarification of structures and responsibilities in their companies as well as more networking and a better publicity for their profession. With regards to the training, respondents desired more practical exercises and case studies. Further research in this field is needed.

[Shaping the future of vocational rehabilitation of adults: eight fields of action as starting points for a cross-actor innovation process]. / Die Zukunft der beruflichen Rehabilitation Erwachsener gestalten: Acht Handlungsfelder als Ausgangspunkt für einen akteursübergreifenden Innovationsprozess.

Established by the Federal Ministry of Labour and Social Affairs (BMAS) in October 2007, the Scientific Expert Group RehaFutur had been commissioned to elaborate cornerstones for the medium- and long-term development of vocational rehabilitation of adults with disabilities (re-integration). Initial questions inter alia were as follows: Which function should vocational rehabilitation have in a service- and knowledge-oriented working world that will increasingly be affected by demographic change? How can disabled persons' right to occupational participation by way of vocational rehabilitation, a right stipulated both under the German constitution and in German law, be realized as needed also in the future? Various fields of action have been derived on the basis, for one, of an investigation of the factors, social law, social and education policy as well as European, influencing vocational rehabilitation and, for the other, of an evaluation of current labour market and demographic developments. Dealt with in the fields of action outlined are the aspects: equitable opportunities of access, developmental and needs orientation, closeness to the real occupational and working world, as well as the role of self-determination and self-responsibility. The fields of action are to be understood as framework concept for shaping a cross-actor innovation process. Sustainable vocational rehabilitation is characterized in particular by the fact that it is specifically targeted at promoting disabled persons' self-determination and self-responsibility actively using these in the process and that it strengthens an independent lifestyle, ensures social participation by inclusive structures; also, it facilitates continued participation in working life by ongoing education involving holistic development of professional and personal competencies oriented towards the individual's resources and potentials, safeguarding it by systematic networking with companies. The concept presented for vocational rehabilitation of adults with disabilities encompasses a change of paradigms which service carriers and providers will have to face jointly and including the service users, the rehabilitants.

Transplanted human cord blood-derived unrestricted somatic stem cells improve left-ventricular function and prevent left-ventricular dilation and scar formation after acute myocardial infarction.

OBJECTIVE: Functional improvement after acute myocardial ischaemia (MI) has been achieved by transplantation of different adult stem and progenitor cell types. It is controversial whether these cell types are able to form novel functional myocardium. Alternatively, graft-related or immune-related paracrine mechanisms may preserve existing myocardium, improve neovascularisation, affect tissue remodelling or induce endogenous de novo formation of functional myocardium. We have applied an alternative somatic cell type, human cord-blood-derived unrestricted somatic stem cells (USSCs) in a porcine model of acute MI. METHODS: USSCs were transplanted into the acutely ischaemic lateral wall of the left ventricle (LV). LV dimension and function were assessed by transoesophageal echocardiography (TEE) pre-MI, immediately post-MI, 48 hours and 8 weeks after USSC injection. Additionally, apoptosis, mitosis and recruitment of macrophages were examined 48 hours post-engraftment. RESULTS: Gender-specific and species-specific FISH/immunostaining failed to detect engrafted donor cells 8 weeks post-MI. Nevertheless, cell treatment effectively preserved natural myocardial architecture. Global left ventricular ejection fraction (LVEF) before MI was 60% (7%). Post-MI, LVEF decreased to 34% (8%). After 8 weeks, LVEF had further decreased to 27% (6%) in the control group and recovered to 52% (2%) in the USSC group (p<0.01). Left-ventricular end-diastolic volume (LVEDV) before MI was 28 (2) ml. 8 weeks post-MI, LVEDV had increased to 77 (4) ml in the control group. No LV dilation was detected in the USSC group (LVEDV: 26 (2) ml, p<0.01). Neither apoptosis nor recruitment of macrophages and mitosis were different in either groups. CONCLUSIONS: Transplantation of USSCs significantly improved LV function and prevented scar formation as well as LV dilation. Since differentiation, apoptosis and macrophage mobilisation at infarct site were excluded as underlying mechanisms, paracrine effects are most likely to account for the observed effects of USSC treatment.

[Suspicion of a newly appearing hypertrophic obstructive cardiomyopathy in a patient treated for hepatocellular carcinoma]. / Verdacht auf neu aufgetretene hypertrophe obstruktive Kardiomyopathie bei hepatozellulärem Karzinom.

HISTORY AND ADMISSION FINDINGS: A 42-year-old women presented with shortness of breath, tachycardia and weakness to our department. Five years ago she had been diagnosed with hepatocellular carcinoma for which an extended hemihepatectomy had been performed. INVESTIGATIONS, DIAGNOSIS AND TREATMENT: The clinical examination revealed a systolic murmur over the artic region. Echocardiography showed an hypertrophed interventricular septum with signs like those in hypertrophic obstructive cardiomyopathy. Ultrasound demonstrated a cystic mass in the pelvis highly suspicious of a metastasis of a hepatocellular carcinoma. Fine needle biopsy confirmed the diagnosis of a metastatic lesion of hepatocellular carcinoma. Computed tomography demonstrated metastase in the lung and a space-occupying in the interventricular septum. The patients underwent resection of the lung and pelvic metastasis and died a few weeks later. CONCLUSION: This case demonstrates the rare occurence of a metastasis to the heart, imitating obstructive cardiac myopathy, in a patient with hepatocellular carcinoma.

Clinically applicable 7-Tesla magnetic resonance visualization of transplanted human adult stem cells labeled with CliniMACS nanoparticles.

BACKGROUND: Intra-myocardial transplantation of bone marrow derived cells is currently under clinical evaluation as a therapy for heart failure. A major limitation of all clinical studies for myocardial restoration through cell transfer is the inability to track the fate of the transplanted cells. We present a clinically applicable technique using advanced ultra high-field 7-Tesla (7T) magnetic resonance imaging (MRI) of nanoparticle-labeled transplanted human EPCs in porcine ischemic hearts. METHODS: CD133 positive cells were isolated from bone marrow by magnetic bead selection. Positive cells (5 - 8 x 10 (6) cells) were transplanted into porcine ischemic myocardium (n = 8). Control animals (n = 3) received a medium injection. MRI on a 7T scanner was performed to demonstrate the distribution of the EPCs. RESULTS: CD133+ cells were identified on gradient echo images (T(1)-weighted) within the myocardium 4 weeks after transplantation. CONCLUSIONS: Magnetically labeled EPCs transplanted for therapeutic neovascularization or reduction of infarct size in myocardial ischemia can be visualized by MRI at high-field strengths.

Multicenter experiences with a single lead electrode for dual chamber ICD systems.

Monitoring of atrial signals improves the accuracy in identifying supraventricular tachyarrhythmias to prevent inappropriate therapies in patients with implantable ICDs. Since difficulties due to the additional atrial lead were found in dual chamber ICD systems with two leads, the authors designed a single pass VDD lead for use with dual chamber ICDs. After a successful animal study, the prototype VDD lead (single coil defibrillation lead with two additional fractally coated rings for bipolar sensing in the atrium) was temporarily used in 30 patients during a German multicenter study. Atrial and ventricular signals were recorded during sinus rhythm (SR), atrial flutter, AF, and VT or VF. The implantation of the lead was successful in 27 of 30 patients. Mean atrial pacing threshold was 2.5 +/- 0.9 V/0.5 ms, mean atrial impedance was 213 +/- 31 ohms. Atrial amplitudes were greater during SR (2.7 +/- 1.6 mV) than during atrial flutter (1.46 +/- 0.3 mV, P < 0.05) or AF (0.93 +/- 0.37 mV, P < 0.01). During VF atrial "sinus" signals had significantly (P < 0.01) lower amplitudes (1.4 +/- 0.52 mV) than during SR. The mean ventricular sensing was 13.3 +/- 7.9 mV and mean ventricular impedance was 577 +/- 64 ohms. Defibrillation was successful with a 20-J shock in all patients. In addition, 99.6% of P waves could be detected in SR and 84.4% of flutter waves during atrial flutter. During AF, 56.6% of atrial signals could be detected without modification of the signal amplifier. In conclusion, a new designed VDD dual chamber lead provides stable detection of atrial and ventricular signals during SR and atrial flutter. Reliable detection of atrial signals is possible without modification of the ICD amplifier.

[The importance of company interests in shaping occupational rehabilitation programs: empirical findings from company-based retraining]. / Die Bedeutung betrieblicher Interessen bei der Gestaltung von Massnahmen der beruflichen Rehabilitation - Empirische Ergebnisse aus der betrieblichen Umschulung.

The pilot project "Occupational Rehabilitation of Women Close to their Place of Residence" is orientated towards the dual system of vocational retraining by combining "on the job training" and "vocational theory in a vocational training school". Training on the job is one of the most important aspects in this programme, and data have therefore been gained from qualitative interviews with representatives of different firms. The results presented are based on the analysis of qualitative interviews with 13 employers involved in the pilot project. All interviewees underline: Training on the job alongside non-disabled persons is thought to offer good opportunities for lasting vocational integration since it enables trainees to grow accustomed to the conditions and demands of work and is thought likely to lead directly to employment. We discussed a range of mechanisms through which a societal obligation to train and/or employ disabled people could be implemented and highlighted the role of "rehabilitation services" which support the trainee by psychological, educational and social services and support the employer.

[Company approaches concerning workers with performance alterations or disablement: interview findings on the perspectives of the various parties involved]. / Betrieblicher Umgang mit der Gruppe leistungsgewandelter und behinderter Mitarbeiter/innen: Befragungsergebnisse aus der Sicht unterschiedlicher Funktionsträger.

This paper provides information about the research programme "In-plant interventions in the German car industry to increase job opportunities for employees with (severe) disabilities". The research was done in 2000 by the University of Trier and the International Research Unit for Work and Social Integration (IFASI). The purpose of the study was to capture, document, and analyse internal practices of occupational rehabilitation in five German car factories. Taking a qualitative approach, 23 persons of different company areas were interviewed, and numerous documents were analysed. The article reflects applied disability management strategies and points out success factors and barriers of inclusion.

Prospective evaluation of catheter ablation in patients with implantable cardioverter defibrillators and multiple inappropriate ICD therapies due to atrial fibrillation and type I atrial flutter.

The high incidence of inappropriate therapies due to drug refractory supraventricular tachycardia remains a major unsolved problem of the ICD. Most of the inappropriate therapies for supraventricular tachycardia are caused by AF and type I atrial flutter with rapid ventricular response. The purpose of this prospective study was to determine the usefulness of AVN modulation or ablation for rapid AF and ablation of the tricuspid annulus-inferior vena cava (TA-IVC) isthmus for type I atrial flutter in ICD patients with frequent inappropriate ICD interventions. Eighteen consecutive patients were enrolled in this study. Twelve patients received a mean of 34 +/- 36 antitachycardia pacing (ATP) and 41 +/- 32 shock therapies for rapid AF during 49 +/- 39 months, and 6 patients a mean of 111 +/- 200 ATP and 11 +/- 8 shock therapies for type I atrial flutter during 52 +/- 37 months preceding ablation procedure. Modification of the AVN was successful in 10 (83%) of 12 AF patients, in 2 (17%) patients ablation of the AVN was performed. A complete TA-IVC isthmus block was achieved in 5 (83%) of 6 atrial flutter patients. Three (25%) AF patients had 11 +/- 24 recurrences of ATP and 0.4 +/- 1.1 shock therapies for rapid AF during 15 +/- 7 months. None of the atrial flutter patients had recurrences of inappropriate therapies for type I atrial flutter during 14 +/- 8 months, but two (33%) patients had inappropriate ICD therapies for type II atrial flutter or rapid AF. There was an overall mean incidence of 18 +/- 22 inappropriate ICD therapies per 6 months before and 4 +/- 9 per 6 months after the ablation procedure (P < 0.05). In conclusion, radiofrequency catheter modification or ablation of the AVN for rapid AF and ablation for atrial flutter type I are demonstrated to be highly effective in the majority of ICD patients with drug refractory multiple inappropriate ICD therapies.

Atrial reentrant tachycardia after surgery for congenital heart disease: endocardial mapping and radiofrequency catheter ablation using a novel, noncontact mapping system.

BACKGROUND: The purpose of the present study was to determine the role of a novel, noncontact mapping system for assessing a variety of atrial reentrant tachycardias (ART) in patients after the surgical correction of congenital heart disease. METHODS AND RESULTS: In 14 patients, an electrophysiological study using the Ensite 3000 system was performed to assess ARTs resistant to medical treatment. Sixteen different forms of ART were inducible in the 14 patients studied. The reentrant circuit of all ARTs could be characterized and localized with respect to anatomic landmarks such as atriotomy scars, intraatrial patches/baffles, and cardiac structures. In 15 of the 16 ARTs (in 13 of the 14 patients), a target area of the reentrant circuit for radiofrequency current application (ie, an area of conduction between 2 anatomical obstacles such as surgical barriers and cardiac structures of electrical isolation) could be localized within the systemic venous atrium. Nine patients exhibited macroreentry, and 4 showed microreentry. In 12 patients, ART could be terminated by creating linear radiofrequency current lesions (75 degrees C, 180 to 390 s). Completeness of linear lesions after radiofrequency current delivery was proven by analyzing color-coded isopotential maps of atrial activation while applying atrial pacing techniques. The mean duration of the procedures was 286 minutes (range, 130 to 435 minutes); fluoroscopy time ranged from 7 to 33.8 minutes (mean, 17.4 minutes). CONCLUSIONS: In patients with ART after the surgical correction of congenital heart disease, the use of the noncontact mapping system allows for characterization of the tachycardia and guidance for effective radiofrequency current delivery.

[Usefulness of a VDD defibrillation electrode in recording atrial electrograms during atrial flutter and atrial fibrillation]. / Nutzen einer VDD-Defibrillationselektrode zur Aufzeichnung von atrialen Elektrogrammen bei Vorhofflimmern/-flattern.

BACKGROUND: Monitoring of atrial signals improves the accuracy in identifying supraventricular tachyarrhythmias to prevent inappropriate therapies in patients with implantable cardioverter-defibrillators (ICD). Since complications due to the additional atrial lead were found in dual chamber ICD systems with 2 leads, we designed a single-pass VDD-lead for use with dual chamber ICDs. PATIENTS AND METHODS: After promising animal experiments in a German multicenter study a prototype VDD lead (single-coil defibrillation electrode with 2 additional fractally coated rings for bipolar sensing in the atrium) was temporarily used in 20 patients. Atrial and ventricular signals were recorded during sinus rhythm, atrial flutter, atrial fibrillation and ventricular tachycardia or ventricular fibrillation. Terminations of ventricular arrhythmias were performed by internal DC shock. RESULTS: The implantation of the electrode was successful in 18 of 20 patients. Mean atrial pacing threshold was 2.45 +/- 0.9 V/0.5 ms, mean atrial impedance was 215 +/- 31 Ohm. Atrial amplitudes were greater during sinus rhythm (2.7 +/- 1.6 mV) than during atrial flutter (1.36 +/- 0.28 mV, p < 0.05) or atrial fibrillation (0.92 +/- 0.29 mV, p < 0.01). During ventricular fibrillation atrial "sinus"-signals had significantly (p < 0.01) lower amplitudes than during sinus rhythm. Mean ventricular sensing was 13.3 +/- 7.9 mV, mean ventricular impedance was 577 +/- 64 Ohm. Defibrillation was successful with 20 J shock. 99.6% of P waves could be detected in sinus rhythm and 85 +/- 9.9% of flutter waves during atrial flutter. During atrial fibrillation 55% of atrial signals could be detected without modification of the signal amplifier. CONCLUSIONS: A new designed VDD dual chamber electrode provides stable detection of atrial and ventricular signals during sinus rhythm and atrial flutter. For reliable detection of atrial fibrillation modifications of the signal amplifier are necessary.

Direct suppressive effects of weak magnetic fields (50 Hz and 16 2/3 Hz) on melatonin synthesis in the pineal gland of Djungarian hamsters (Phodopus sungorus).

In many investigations performed thus far on rodents, a suppression of melatonin synthesis was observed when animals were exposed to weak magnetic fields. However, among the several issues not yet resolved is the question of whether the observed changes are caused by direct effects on the pineal gland or by indirect effects, e.g., at the level of the eyes. We, therefore, performed a series of experiments in which direct effects of weak magnetic fields were studied in isolated pineal glands of Djungarian hamsters (Phodopus sungorus). After sacrifice of animals during morning hours, pineal glands were removed and placed individually into glass chambers that were perfused with oxygenated buffer. Experiments (n = 8) lasted for 8 hr. Magnetic fields (1,623 or 50 Hz at 86 microTesla) were generated by Helmholtz coils, and were present during the entire period. In each experiment, 12 exposed, and 12 sham-exposed, pineal glands were placed individually in glass chambers, which were surrounded by identical coils. Because of the design of the coils (bifilament), and the experimental setup (black box), the experimentator was not aware which coil was activated until the results were obtained. After 3.25 hr of adaptation, melatonin production was stimulated by isoproterenol (10(-7) M) for 30 min. Eluted fractions were collected, and melatonin concentrations were measured by radioimmunoassay. Maximum melatonin production was achieved after 5-7 hr. In all experiments, maximum melatonin concentrations were lower in the exposed groups compared with the sham-exposed controls. Statistical analyses for each frequency showed significant suppressive effects at 16(2/3) Hz (P < 0.01), and 50 Hz (P < 0.00). It is concluded that the suppressive effects of magnetic fields on the synthesis of melatonin are a result of primary mechanisms at the level of the pineal gland.

Lactoferrin and eosinophilic cationic protein in nasal secretions of patients with experimental rhinovirus colds, natural colds, and presumed acute community-acquired bacterial sinusitis.

To distinguish sinusitis from uncomplicated "colds," we examined lactoferrin and eosinophilic cationic protein (ECP) in nasal secretions. Lactoferrin titers were >/=1:400 in 4% of persons with uncomplicated colds and controls but in 79% of persons with sinusitis or purulent sputa. ECP levels were >200 ng/ml in 61% of persons with colds and >3,000 ng/ml in 62% of persons with sinusitis. Nasal lactoferrin helps distinguish sinusitis from colds.