[Differential diagnosis of hoarseness]. / Differenzialdiagnostik der Heiserkeit.

Hoarseness can be the leading symptom of dysphonia. In combination with impaired vocal performance and subjective voice-related discomfort, it can represent an individually different handicap for patients and lead to limited participation in social and professional life. Since the reasons for dysphonia may be not only functional but also organic with a potentially poor prognosis, hoarseness must be clarified using differential diagnosis. In addition to the knowledge of possible diseases, pathogenesis, and treatment options for dysphonia, the differential diagnostic approach requires profound knowledge of the various diagnostic methods, and of the interpretation of the results in particular. The etiology of dysphonia is very diverse and rarely monocausal. Therefore, a team-based and interdisciplinary differential diagnostic approach is recommended.

Intracutaneously injected human adipose tissue-derived stem cells in a mouse model stay at the site of injection.

The aim of this study was to evaluate the local behavior of intracutaneously injected human mesenchymal stem cells from adipose tissue and to determine the safety of a cell-based cutaneous therapy in an animal model.Human mesenchymal stem cells from adipose tissue were labeled with red fluorochrome and were injected intradermally in the paravertebral area in immunodeficient BalbC/nude mice (n = 21). As a control, cell culturemedium was injected in the same fashion on the contralateral paravertebral side. Four weeks, 6 months, and 12 months after the injection, seven mice were examined. In addition to the injected areas, the lungs, kidneys,spleens, and brains were excised and processed for histological evaluation. Serial sections of all the tissues excised were evaluated for adipose tissue-derived stem cells by means of emerging red fluorescent signals.The injected stem cells could be detected throughout the follow-up period of 1-year at the injection site within the dermal and subcutaneous layers. Bar these areas, adipose tissue-derived stem cells were not found in any otherexamined tissue at any point in time. The adipose tissue-derived stem cells showed a slow transition to deeper subcutaneous adipose tissue layers and, in part, a differentiation into adipocytes. No ulceration, inflammation, ortumor induction could be detected.The present study shows that intracutaneously injected human mesenchymal stem cells from adipose tissue stay at the site of injection, survive in vivo for up to 1-year, and partly differentiate into adipocytes. This is a new andvery important finding needed to safely apply therapies based on such stem cells in fat transplants in regenerative medicine.

Biocompatibility of poly(ethylene glycol)-based hydrogels in the brain: an analysis of the glial response across space and time.

Poly(ethylene glycol) or PEG-based hydrogels provide a useful methodology for tissue engineering and the controlled-release of drugs within the central nervous system (CNS). To be successful, the local neuroinflammatory response to an implant must be well understood. Toward this end, the focus was to examine the localized recruitment and activation of microglia and astrocytes following implantation of PEG-based hydrogels in the brain. Because they are of clinical relevance and may impact brain tissue differently, hydrogels with different mass loss profiles were examined. At all time points, a needle penetration in sham animals evoked a greater astrocytic response than hydrogel conditions. The astrocyte response that ensued varied with degradation rate. An attenuated response was present in more slowly degrading and nondegrading conditions. Relative to sham, hydrogel conditions attenuated the acute microglial response during the week after implant. By 56 days, microglial levels in shams decreased below the observed response in slowly degrading and nondegradable gels, which remained constant overtime. Although the inflammatory response to PEG-based hydrogels was complex depending on degradation rates, the magnitude of the acute microglia response and the long-term astrocyte response were attenuated suggesting the use of these materials for drug and cell delivery to the CNS.

Biocompatibility of PEG-based hydrogels in primate brain.

Degradable polymers have been used successfully in a wide variety of peripheral applications from tissue regeneration to drug delivery. These polymers induce little inflammatory response and appear to be well accepted by the host environment. Their use in the brain, for neural tissue reconstruction or drug delivery, also could be advantageous in treating neurodegenerative disorders. Because the brain has a unique immune response, a polymer that is compatible in the body may not be so in the brain. In the present study, polyethylene glycol (PEG)-based hydrogels were implanted into the striatum and cerebral cortex of nonhuman primates. Four months after implantation, brains were processed to evaluate the extent of astrogliosis and scaring, the presence of microglia/macrophages, and the extent of T-cell infiltration. Hydrogels with 20% w/v PEG implanted into the brain stimulated a slight increase in astrocytic and microglial/macrophage presence, as indicated by a small increase in glial fibrillary acidic protein (GFAP) and CD68 staining intensity. This increase was not substantially different from that found in the sham-implanted hemispheres of the brain. Staining for CD3+ T cells indicated no presence of peripheral T-cell infiltration. No gliotic scarring was seen in any implanted hemisphere. The combination of low density of GFAP-positive cells and CD68-positive cells, the absence of T cells, and the lack of gliotic scarring suggest that this level of immune response is not indicative of immunorejection and that the PEG-based hydrogel has potential to be used in the primate brain for local drug delivery or neural tissue regeneration.

Neuropsychological and behavioural disinhibition in adult ADHD compared to borderline personality disorder.

BACKGROUND: Although attention-deficit/hyperactivity disorder (ADHD) is thought to be an inhibitory disorder, the question remains of how specific the inhibitory deficit is in adults and whether it distinguishes ADHD from borderline personality disorder (BPD), with which it shares several clinical features, particularly impulsiveness. METHOD: The study assessed various motor and cognitive inhibitory functions (inhibition of prepotent, ongoing and interfering responses) in addition to working memory in adult ADHD patients with and without BPD, compared to subjects with BPD alone and controls. In addition, questionnaire data on various aspects of impulsiveness and anger regulation were assessed in all groups. RESULTS: ADHD patients performed worse than BPD individuals and controls in two inhibitory tasks: the stop signal task and the conflict module of the Attentional Network Task (ANT). In addition, they exhibited longer reaction times (RTs) and higher intra-individual variance in nearly all attentional tasks. The co-morbid group exhibited poor performance on the stop signal task but not on the conflict task. The BPD group barely differed from controls in neuropsychological performance but overlapped with ADHD in some behavioural problems, although they were less severe on the whole. CONCLUSIONS: Impaired inhibition is a core feature in adults with ADHD. In addition, slow RTs and high intra-individual variance in performance may reflect deficits in the regulation of activation and effort in ADHD patients. ADHD and BPD share some symptoms of behavioural dysregulation without common cognitive deficits, at least in the attentional realm.

Synergy between medical informatics and bioinformatics: facilitating genomic medicine for future health care.

In this paper, we review the results of BIOINFOMED, a study funded by the European Commission (EC) with the purpose to analyse the different issues and challenges in the area where Medical Informatics and Bioinformatics meet. Traditionally, Medical Informatics has been focused on the intersection between computer science and clinical medicine, whereas Bioinformatics have been predominantly centered on the intersection between computer science and biological research. Although researchers from both areas have occasionally collaborated, their training, objectives and interests have been quite different. The results of the Human Genome and related projects have attracted the interest of many professionals, and introduced new challenges that will transform biomedical research and health care. A characteristic of the 'post genomic' era will be to correlate essential genotypic information with expressed phenotypic information. In this context, Biomedical Informatics (BMI) has emerged to describe the technology that brings both disciplines (BI and MI) together to support genomic medicine. In recognition of the dynamic nature of BMI, institutions such as the EC have launched several initiatives in support of a research agenda, including the BIOINFOMED study.

Auditory-evoked potentials and selective attention: different ways of information processing in cannabis users and controls.

The present study tested the hypothesis that chronic cannabis use leads to persistent attentional dysfunctions and that age of onset of cannabis use is a potential predictor of impaired test performance and information processing. Brain event-related potentials (ERPs) during a complex auditory selective attention task were recorded from 21 cannabis users divided into two groups according to age of onset and from 13 controls comparable with respect to age, IQ and educational background. Participants were instructed to detect target tones of a particular location, pitch and duration from a total sample of random frequencies. The study reveals that the latency of the greatest negative peak of ERPs (200 and 300 ms) to target tones was shorter in controls, while there was no clear difference between target and non-target within cannabis users. In addition, users displayed a reduced P3 to target tones. This was more pronounced in early-onset cannabis users. These data suggest that chronic cannabis use relates to different types of information processing under conditions of selective attention. There is some evidence that users employed different strategies of attention allocation. The results are discussed with respect to possible underlying mechanisms and clinical implications.

Internet health resources: from quality to trust.

OBJECTIVES: Quality of online health resources remains a much debated topic, despite considerable international efforts. The lack of a systematic and comprehensive conceptual analysis is hindering further progress. Therefore we aim at clarifying the origins, nature and interrelations of pertinent concepts. Further, we claim that quality is neither a necessary nor a sufficient condition for Internet health resources to produce an effect offline. As users' trust is also required, we examine the relation of quality aspects to trust building online. METHODS: We reviewed and analyzed the key documentation and deliverables of quality initiatives, as well as relevant scientific publications. Using the insights of philosophy, we identified the elementary dimensions which underlie the key concepts and theories presented so far in the context of online health information quality. We examined the interrelations of various perspectives and explored how trust as a phenomenon relates to these dimensions of quality. RESULTS: Various aspects associated with the quality of online health resources originate from four conceptual dimensions: epistemic, ethical, economic and technological. We propose a conceptual framework that incorporates all these perspectives. We argue that total quality exists only if all four dimensions have been addressed adequately and that high total quality is conducive to warranted trust. CONCLUSIONS: Quality and trust are intertwined, but distinct concepts, and their relation is not always straightforward. Ideally, trust should track quality. Apprehending the composition of these concepts will help to understand and guide the behavior of both users and providers of online information, as well as to foster warranted trust in online resources. The framework we propose provides a conceptual starting point for further deliberations and empirical work.

A framework for improving the quality of health information on the world-wide-web and bettering public (e-)health: the MedCERTAIN approach.

There has been considerable debate about the variable quality of health information on the world-wide-web and its impact on public health. While central authorities to regulate, control, censor, or centrally approve information, in-formation providers or websites are neither realistic nor desirable, public health professionals are interested in making systems available that direct patient streams to the best available information sources. National governments and medical societies have also recognized their responsibility to help users to identify "good quality" information sources. But what constitutes good quality, and how can such a system be implemented in a decentralized and democratic manner? This paper presents a model which combines aspects of consumer education, encouragement of best practices among information providers, self-labeling and external evaluations. The model is currently being implemented and evaluated in the MedCERTAIN project, funded by the European Union under the Action Plan for Safer Use of the Internet. The aim is to develop a technical and organisational infrastructure for a pilot system that allows consumers to access metainformation about web-sites and health information providers, including disclosure information from health providers and opinions of external evaluators. The paper explains the general conceptual framework of the model and presents preliminary experiences including results from an expert consensus meeting, where the framework was discussed.

Cytotoxic necrotizing factor type 1-positive Escherichia coli causes increased inflammation and tissue damage to the prostate in a rat prostatitis model.

Infection of rat prostates with cytotoxic necrotizing factor type 1 (CNF1)-positive uropathogenic Escherichia coli caused more inflammation-mediated morphological and histological tissue damage than did infection with isogenic CNF1-negative mutants. These striking differences occurred despite the finding that bacterial counts for the strain pairs were indistinguishable. We conclude that CNF1 contributes to E. coli virulence in a model of acute prostatitis. To our knowledge, the results of this study provide the first demonstration of a role for any uropathogenic E. coli virulence factor in acute prostatitis.

A comparative in vitro study of a magnetostrictive and a piezoelectric ultrasonic scaling instrument.

BACKGROUND: The effects of magnetostrictive ultrasonic instruments and piezoelectric ultrasonic instruments on tooth surfaces seem to differ with regards to root debridement. AIM: The purpose of this study was to compare a magnetostrictive ultrasonic scaling instrument with a piezoelectric ultrasonic scaling instrument and a hand curette regarding time taken, calculus removal, tooth surface roughness (Ra), and SEM examination before and after instrumentation. METHODS: 30 extracted human teeth with subgingival calculus were assigned to one of three treatment groups (n=10). The working force was standardised for both ultrasonic instruments at 200 g and for the curette at 500 g. RESULTS: The results revealed that the time needed for instrumentation was 126.1+/-38.2 s for the curette, significantly more than for the piezoelectric ultrasonic instrument (74.1+/-27.6 s; p<0.05) and 104.9+/-25.4 s for the magnetostrictive ultrasonic instrument. Remaining calculus was similar for all three groups. The end Ra values were significantly worse for the piezoelectric instrument (2.02+/-0.41; p<0.05) compared to 1.42+/-0.48 for the curette and 1.36+/-0.41 for the magnetostrictive instrument. The SEM examination revealed the smoothest surfaces but, subjectively, the most tooth substance loss after the curette, followed by the magnetostrictive instrument, with the least substance loss, and then the piezoelectric instrument, with medium substance loss. CONCLUSION: The piezoelectric ultrasonic scaler was more efficient than the magnetostrictive ultrasonic scaler in removing calculus but left the instrumented tooth surface rougher.

Mutation of the gene encoding cytotoxic necrotizing factor type 1 (cnf(1)) attenuates the virulence of uropathogenic Escherichia coli.

Cytotoxic necrotizing factor type 1 (CNF1) is a 115-kDa toxin that activates Rho GTPases and is produced by uropathogenic Escherichia coli (UPEC). While both epidemiological studies that link CNF1 production by E. coli with urinary tract disease and the cytopathic effects of CNF1 on cultured urinary tract cells are suggestive of a role for the toxin as a UPEC virulence factor, few in vivo studies to test this possibility have been reported. Therefore, in this investigation, we evaluated the importance of CNF1 in a murine model of urinary tract infection (UTI) by comparing the degree of colonization and damage induced by three different CNF1-producing E. coli strains with isogenic CNF1-deficient derivatives. The data from single-strain challenge experiments with C3H/HeOuJ mice indicated a trend toward higher counts of the wild-type strains in the urine and bladders of these animals up to 3 days after challenge in two of three strain pairs. Furthermore, this difference was statistically significant at day 2 of infection with one strain pair, C189 and C189cnf(1). To control for the animal-to-animal variability inherent in this model, we infected C3H/HeOuJ mice with a mixture of CNF1-positive and -negative isogenic derivatives of CP9. The CNF1-positive strain was recovered in higher numbers than the CNF1-negative strain in the urine, bladders, and kidneys of the mice up to 9 days postinfection. These striking coinfection findings, taken with the trends observed in single-strain infections, led us to conclude that CNF1-negative strains were generally attenuated compared to the wild type in the C3H/HeOuJ mouse model of UTI. Furthermore, histopathological examination of bladder specimens from mice infected with CNF1-positive strains consistently showed deeper, more extensive inflammation than in those infected with the isogenic mutants. Lastly, we found that CNF1-positive strain CP9 was better able to resist killing by fresh human neutrophils than were CP9cnf(1) bacteria. From these data in aggregate, we propose that CNF1 production increases the capacity of UPEC strains to resist killing by neutrophils, which in turn permits these bacteria to gain access to deeper tissue and persist better in the lower urinary tract.

A metadata vocabulary for self- and third-party labeling of health web-sites: Health Information Disclosure, Description and Evaluation Language (HIDDEL).

We describe HIDDEL (Health Information Disclosure, Description and Evaluation Language), formerly known as medPICS (platform for Internet content selection in medicine), a metadata vocabulary designed to enhance transparency, trust and quality of health information on the web. The vocabulary may be used (1) by webmasters to self-describe their contents and policies; (2) by infomediaries (e.g. Healthfinder, NHS Direct/NeLH), e.g. third party evaluators, rating or portal services, to annotate other websites; (3) and by users, to describe their preferences. As an XML application it conforms to the W3C's RDF Specification. The metadata vocabulary is primarily intended to enable descriptions of whole health websites or health information providers. The vocabulary is designed to provide a computer-readable electronic "label" of a health website, telling users who is behind the website, how the website is sponsored, what the con-tent, aim and target audience is, how the information was compiled, what risks the service bears, or what people say about the resource. Client-software can "read" this label automatically, compare it to the user s own set of preferences and needs, and alert and advise users.

MedCERTAIN: quality management, certification and rating of health information on the Net.

MedCERTAIN (MedPICS Certification and Rating of Trustworthy Health Information on the Net, http://www.medcertain.org/) is a recently launched international project funded under the European Union's (EU) "Action Plan for safer use of the Internet. It provides a technical infrastructure and a conceptual basis for an international system of "quality seals", ratings and self-labelling of Internet health information, with the final aim to establish a "trustmark" for networked health information. Digital "quality seals" are evaluative metadata (using standards such as PICS = Platform for Internet Content Selection, now being replaced by RDF/XML) assigned by trusted third-party raters. The project also enables and encourages self-labelling with descriptive meta-information by web authors. Together these measures will help consumers as well as professionals to identify high-quality information on the Internet. MedCERTAIN establishes a fully functional demonstrator for a self- and third-party rating system enabling consumers and professionals to filter harmful health information and to positively identify and select high quality information. We aim to provide a system which allows citizens to place greater trust in networked information, exemplified in the domain of health information, whilst also making a significant contribution for similar projects with different target domains. The project will demonstrate how PICS-based content rating and filtering technologies can automate and exploit value-adding resource description services. It further proposes standards for interoperability of rating services.

EU-project medCERTAIN: Certification and Rating of Trustworthy and Assessed Health Information on the Net.

Med-CERTAIN (MedPICS Certification and Rating of Trustworthy Health Information on the Net, http://www.medpics.org/medcertain/) is a recently launched project funded under the EU Action Plan for safer use of the Internet. It will provide the technical infrastructure for an international system of "quality seals" for Internet health information. Digital "quality seals" may be evaluative metainformation (using standards such as PICS = Platform for Internet Content Selection, now being replaced by RDF/XML) assigned by trusted third-party raters. The project will also enable and encourage self-labelling with descriptive metainformation by web authors. Together these measures will help consumers to identify high-quality information on the Internet. Med-CERTAIN will establish a fully functional demonstrator for a self- and third-party rating system enabling patients and consumers to filter harmful health information and to positively identify and select high quality information. We aim to provide a system allow European citizens to place greater trust in networked information, exemplified in the domain of health information, whilst also making a significant contribution for similar projects with different target domains. The project will demonstrate how PICS-based content rating and filtering technologies can automate and exploit value-adding resource description services. The proposed technology strategy combines a pragmatic use of simple existing technologies for data acquisition with a future-oriented standards policy intended to lead rather than follow the evolution of definitions for information-mediation services.

Quality management, certification and rating of health information on the Net with MedCERTAIN: using a medPICS/RDF/XML metadata structure for implementing eHealth ethics and creating trust globally.

MedCERTAIN (MedPICS Certification and Rating of Trustworthy Health Information on the Net, http://www.medcertain.org/) is a recently launched international project funded under the European Union's (EU) "Action Plan for safer use of the Internet". It provides a technical infrastructure and a conceptual basis for an international system of "quality seals", ratings and self-labelling of Internet health information, with the final aim to establish a global "trustmark" for networked health information. Digital "quality seals" are evaluative metadata (using standards such as PICS=Platform for Internet Content Selection, now being replaced by RDF/XML) assigned by trusted third-party raters. The project also enables and encourages self-labelling with descriptive metainformation by web authors. Together these measures will help consumers as well as professionals to identify high-quality information on the Internet. MedCERTAIN establishes a fully functional demonstrator for a self- and third-party rating system enabling consumers and professionals to filter harmful health information and to positively identify and select high quality information. We aim to provide a trustmark system which allows citizens to place greater confidence in networked information, to encourage health information providers to follow best practices guidelines such as the Washington eHealth Code of Ethics, to provide effective feedback and law enforcement channels to handle user complaints, and to stimulate medical societies to develop standard for patient information. The project further proposes and identifies standards for interoperability of rating and description services (such as libraries or national health portals) and fosters a worldwide collaboration to guide consumers to high-quality information on the web.

Mushroom toxicology resources utilized by certified regional poison centers in the United States.

A survey of certified regional poison centers in the United States was performed to determine sources of treatment information for mushroom intoxications, and extent of reporting of mushroom epidemiological data to a national mushroom case registry.