Search

RM; Trastornos hereditarios de neurotransmisores; Monoaminas; Deficiencia de tetrahidrobiopterina RM; Trastorns dels neurotransmissors heretats; Monoamines; Deficiència de tetrahidrobiopterina MRI; Inherited neurotransmitter disorders; Monoamines; Tetrahydrobiopterin deficiency; Inherited monoamine neurotransmitter disorders (iMNDs) are rare disorders with clinical manifestations ranging from mild infantile hypotonia, movement disorders to early infantile severe encephalopathy. Neuroimaging has been reported as non-specific. We systematically analyzed brain MRIs in order to characterize and better understand neuroimaging changes and to re-evaluate the diagnostic role of brain MRI in iMNDs. 81 MRIs of 70 patients (0.1-52.9 years, 39 patients with tetrahydrobiopterin deficiencies, 31 with primary disorders of monoamine metabolism) were retrospectively analyzed and clinical records reviewed. 33/70 patients had MRI changes, most commonly atrophy (n = 24). Eight patients, six with dihydropteridine reductase deficiency (DHPR), had a common pattern of bilateral parieto-occipital and to a lesser extent frontal and/or cerebellar changes in arterial watershed zones. Two patients imaged after acute severe encephalopathy had signs of profound hypoxic-ischemic injury and a combination of deep gray matter and watershed injury (aromatic l-amino acid decarboxylase (AADCD), tyrosine hydroxylase deficiency (THD)). Four patients had myelination delay (AADCD; THD); two had changes characteristic of post-infantile onset neuronal disease (AADCD, monoamine oxidase A deficiency), and nine T2-hyperintensity of central tegmental tracts. iMNDs are associated with MRI patterns consistent with chronic effects of a neuronal disorder and signs of repetitive injury to cerebral and cerebellar watershed areas, in particular in DHPRD. These will be helpful in the (neuroradiological) differential diagnosis of children with unknown disorders and monitoring of iMNDs. We hypothesize that deficiency of catecholamines and/or tetrahydrobiopterin increase the incidence of and the CNS susceptibility to vascular dysfunction.

BACKGROUND: Laboratory investigations of cerebrospinal fluid (CSF) are essential when suspecting an inborn error of metabolism (IEM) involving neurological features. Available tests are currently performed on different analytical platforms, requiring a large sample volume and long turnaround time, which often delays timely diagnosis. Therefore, it would be preferable to have an "one-instrument" targeted multi-metabolite approach. METHOD: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform, based on two different methods for analysing 38 metabolites using positive and negative electrospray ionisation modes, was established. To allow for platform extension, both methods were designed to use the same CSF sample preparation procedure and to be run on the same separation column (ACE C18-PFP). RESULTS: Assessment of the LC-MS/MS platform methods was first made by analytical validation, followed by the establishment of literature-based CSF cut-off values and reference ranges, and by the measurement of available samples obtained from patients with confirmed diagnoses of aromatic l-amino acid decarboxylase deficiency, guanidinoacetate methyltransferase deficiency, ornithine aminotransferase deficiency, cerebral folate deficiency and methylenetetrahydrofolate reductase deficiency. CONCLUSION: An extendable targeted LC-MS/MS platform was developed for the analysis of multiple metabolites in CSF, thereby distinguishing samples from patients with IEM from non-IEM samples. Reference concentrations for several biomarkers in CSF are provided for the first time. By measurement on a single analytical platform, less sample volume is required (200 µL), diagnostic results are obtained faster, and preanalytical issues are reduced. SYNOPSIS: LC-MS/MS platform for CSF analysis consisting of two differentially designed methods.

Low protein diet and sodium or glycerol phenylbutyrate, two pillars of recommended long-term therapy of individuals with urea cycle disorders (UCDs), involve the risk of iatrogenic growth failure. Limited evidence-based studies hamper our knowledge on the long-term effects of the proposed medical management in individuals with UCDs. We studied the impact of medical management on growth and weight development in 307 individuals longitudinally followed by the Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD). Intrauterine growth of all investigated UCDs and postnatal linear growth of asymptomatic individuals remained unaffected. Symptomatic individuals were at risk of progressive growth retardation independent from the underlying disease and the degree of natural protein restriction. Growth impairment was determined by disease severity and associated with reduced or borderline plasma branched-chain amino acid (BCAA) concentrations. Liver transplantation appeared to have a beneficial effect on growth. Weight development remained unaffected both in asymptomatic and symptomatic individuals. Progressive growth impairment depends on disease severity and plasma BCAA concentrations, but cannot be predicted by the amount of natural protein intake alone. Future clinical trials are necessary to evaluate whether supplementation with BCAAs might improve growth in UCDs.

To improve our understanding of urea cycle disorders (UCDs) prospectively followed by two North American (NA) and European (EU) patient cohorts.

Individuals with urea cycle disorders (UCDs) often present with intellectual and developmental disabilities. The major aim of this study was to evaluate the impact of diagnostic and therapeutic interventions on cognitive outcomes in UCDs.

Aromatic L-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurometabolic disorder that leads to a severe combined deficiency of serotonin, dopamine, norepinephrine and epinephrine. Onset is early in life, and key clinical symptoms are hypotonia, movement disorders (oculogyric crisis, dystonia, and hypokinesia), developmental delay, and autonomic symptoms. In this consensus guideline, representatives of the International Working Group on Neurotransmitter Related Disorders (iNTD) and patient representatives evaluated all available evidence for diagnosis and treatment of AADCD and made recommendations using SIGN and GRADE methodology. In the face of limited definitive evidence, we constructed practical recommendations on clinical diagnosis, laboratory diagnosis, imaging and electroencephalograpy, medical treatments and non-medical treatments. Furthermore, we identified topics for further research. We believe this guideline will improve the care for AADCD patients around the world whilst promoting general awareness of this rare disease.

BACKGROUND Substantial differences exist between traditionally cooked and chemically designed ready-to-serve products and raise questions about the general principles and requirements of current food law. METHODS Differences in amino acid patterns were analyzed in four examples of chicken preparations (boiled chicken meat, traditionally prepared broth from whole chicken, and two commercial chicken broths), and four examples of vegetable broth (traditionally prepared, two commercial products one of which was claimed a BIO-product, and the classic German bouillon cube). RESULTS Chicken meat contained 284 mg of free amino acids in 100 ml of the boiled meat homogenate, with physiological peaks of glutamate (14.5 mg/100 ml), glutamine (8.5 mg/100 ml), anserine (88 mg/100 ml) and carnosine (55 mg/100 ml). The patterns significantly differ in industrially designed chicken soups with elevated peaks of glutamate, and missing anserine or carnosine. Similar results were obtained in vegetable broths. In the classic German bouillon cube, glutamate accounts for 96% of all free amino acids. CONCLUSIONS The amino acid composition of modern ready-to-serve chicken soups and vegetable broths are far from being similar to any natural composition. We need to question current legal definitions of food, and consider its impact on eating habits, appetite regulation and obesity.

Fragestellung: Derzeit wird am Zentrum für Kinder- und Jugendmedizin Heidelberg ein interprofessionelles Blended Learning-Konzept, bestehend aus Virtuellen Patienten, Online-Diskussion und praktischem Training für Ärzte und Pflegekräfte entwickelt, um beide Berufsgruppen besser a[for full text, please go to the a.m. URL], Jahrestagung der Gesellschaft für Medizinische Ausbildung (GMA)

Fragestellung: Virtuelle Patienten (VP) werden zunehmend in der medizinischen Ausbildung eingesetzt. Allerdings ist die Datenlage zu folgenden Fragestellungen spärlich [ref:1]: Lehren: Was sind Faktoren, um als Lehrender VP an der eigenen Institution erfolgreich zu etablieren?[for full text, please go to the a.m. URL], Jahrestagung der Gesellschaft für Medizinische Ausbildung (GMA)

Free amino acids affect food palatability. As information on amino acids in frequently purchased pre-packaged food is virtually absent, we analyzed free amino acid patterns of 17 frequently purchased ready-to-serve convenience food products, and compared them with the information obtained from the respective food labels.Quantitative amino acid analysis was performed using ion-exchange chromatography. gamma-Aminobutyric acid (GABA) concentrations were verified using a stable isotope dilution gas chromatography/mass spectrometry (GC-MS) method. The patterns of free amino acids were compared with information obtained from food labels.An obvious mismatch between free amino acid patterns and food label information was detected. Even on considering that tomatoes and cereal proteins are naturally rich in glutamate, the concentrations of free glutamate outranged the natural concentration of this amino acid in several products, and strongly suggested artificial enrichment. Free glutamate was found to be elevated even in dishes that explicitly state 'no glutamate added'. Arginine was markedly elevated in lentils. Free cysteine was generally low, possibly reflecting thermal destruction of this amino acid during food processing. The meat and brain-specific dipeptide carnosine (CARN) was present in most meat-containing products. Some products did not contain detectable amounts of CARN in spite of meat content being claimed on the food labels. We detected GABA at concentrations that contribute significantly to the taste sensation.This investigation highlights a marked mismatch between food label information and food composition.

[for full text, please go to the a.m. URL], Research in Medical Education - Chances and Challenges 2009

[for full text, please go to the a.m. URL], Research in Medical Education - Chances and Challenges 2009

[for full text, please go to the a.m. URL], Research in Medical Education - Chances and Challenges 2009

Introduction: Communicative competence is essential for daily medical routine. The usefulness of communication-trainings for physicians is described in various publications. However, specific trainings in paediatrics are rarely found. A characteristic for paediatric work is that the primary communication is not only with the patient - the child - but also with the parents. Beside self-assessment external assessment by parents can be used for evaluation of paediatrician's communicative skills.Methods: 28 paediatric residents (intervention group n = 14; control group n = 14) of the University Children's Hospital of Heidelberg took part in a communication training using standardised parents and -patients (SP), video recording and feedback by peers, SPs and supervisors. Data of self-evaluated communicative competence in contact with parents was collected from all participants before and after the training of the intervention group. In addition there was an assessment of parents' satisfaction with the paediatricians-parents communication concerning their children's treatment nine weeks before and nine weeks after the training (n = 248). A follow-up survey to record the transfer into clinical practice was conducted with the participants after six months.Results: After the training participants of the intervention group showed an increased feeling of communicative competence in reference to communicative situations that were explicitly practiced in the training. The external assessment by parents generally showed a positive evaluation of paediatricians' communication skills. However, a group effect was not found. In the follow-up survey participants reported an improved self-perception and specific elements of the training that facilitated the daily clinical practice with parents and their children. Discussion: The training of specific relevant clinical situations lead to an increase in perceived communicative competence and competence in handling difficult encounters with parents. Communication trainings should be integrated not only into the medical student education but also into post-graduate education curricula. Einführung: Kommunikative Kompetenzen sind wesentlich für den ärztlichen Alltag. In der Literatur wird vielfach der Nutzen von Kommunikationsschulungen für Ärzte beschrieben, über gezielte Schulungen für den Fachbereich Pädiatrie finden sich nur vereinzelt Berichte. Die Besonderheit der pädiatrischen Versorgung besteht dabei im Wesentlichen darin, dass nicht nur die Kommunikation zum Patienten - dem Kind -, sondern auch zu dessen Eltern oder Bezugspersonen eine entscheidende Rolle spielt. Zur Überprüfung kommunikativer Fähigkeiten von Pädiatern können neben Selbsteinschätzungen auch Fremdeinschätzungen durch Eltern dienen.Methode: 28 Assistenzärzte (Interventionsgruppe n = 14; Kontrollgruppe n = 14) der Universitätsklinik für Kinder- und Jugendmedizin in Heidelberg nahmen an einer Kommunikationsschulung teil. Diese beinhaltete Übungsgespräche mit standardisierten Eltern und -Patienten (SP), Videoaufzeichnungen sowie Feedback von SPs, Peers und Supervisoren. Daten zur Selbsteinschätzung der eigenen kommunikativen Kompetenz wurden vor und nach der Schulung der Interventionsgruppe von allen Teilnehmern erhoben. Weiterhin wurde neun Wochen vor und neun Wochen nach Abschluss der Schulung eine Elternbefragung bei n = 248 Eltern durchgeführt, in der die Zufriedenheit mit dem Arztkontakt hinsichtlich der Arzt-Eltern Kommunikation erfasst wurde. Nach 6 Monaten schloss sich eine Nachbefragung bei den Teilnehmern zum Transfer in den Klinikalltag an.Ergebnis: Bei den Teilnehmern der Interventionsgruppe zeigte sich im Gegensatz zur Kontrollgruppe nach Abschluss der Schulung eine signifikante Steigerung der subjektiven Kompetenzeinschätzung in Bezug auf die kommunikativen Situationen, die speziell in der Schulung trainiert wurden. Die Fremdeinschätzung durch die Eltern ergab eine generell sehr positive Bewertung der Ärzte, es ließ sich jedoch kein Gruppeneffekt nachweisen. Im Langezeitverlauf berichteten die Teilnehmer von einer verbesserten Selbstwahrnehmung und benannten konkrete Elemente der Schulung, die ihnen die tägliche klinische Arbeit im Kontakt mit Eltern erkrankter Kinder erleichterten.Diskussion: Das Training von spezifischen, für den klinischen Alltag typischen Situationen führt zu einer Verbesserung der Selbsteinschätzung kommunikativer Kompetenzen bezüglich des Umgangs mit schwierigen Situationen im Elternkontakt. Eine Integration von Kommunikationsschulungen nicht nur in das Medizinstudium, sondern auch in postgraduierte Ausbildungs-Curricula erscheint daher sinnvoll.

Introduction: "Standardised patients" are finding increased application within medical training and have become an indispensable component of communication training for medical students. In the Anglo-American world, "standardised patients" are also employed in the postgraduate curriculum for resident physicians. In the German-speaking realm, however, there are currently no publications indicating the use of "standardised parents" in the specialist field of paediatrics. The basic recurring question concerning the extent to which training with "standardised parents" can be considered adequately realistic - a question which has already been raised in connection with the use of "standardised patients" - is of particular relevance in the case of highly experienced clinical staff. The degree to which feedback from "standardised parents" proves helpful in everyday clinical life also remains to be ascertained. Methods: In the current project, a communication training course involving "standardised patients", who simulated the parents and caregivers of ill children, was carried out with residents of Heidelberg University Clinic for Paediatric and Adolescent Medicine. 28 Accident and Emergency were trained in dealing with problems and difficult situations arising in communication with parents. Following the physician-parent dialogue, the respective physician received feedback from the actors, fellow medical peers and supervisors. The authenticity of the cases and their relevance in the context of a realistic training course for communication skills was assessed by means of a questionnaire for participants. Additionally, participants evaluated the quality of the feedback received following the physician-parent dialogue. Results: Physicians considered the training cases to be extremely authentic and of relevance regarding both the improvement of communication skills and confidence in dealing with the parents of ill children. Feedback from actors (Likert scale: M = 1.08; SD = 0.28), from supervisors (M = 1.25; SD = 0.68) and medical peers (M =1.29; SD = 0.55) received very high ratings. Discussion: In the project presented here, the application of "standardised parents" represents a valuable tool which can be considered a suitable and obligatory component within a structured communication training course for paediatric residents. Furthermore, the employment of "standardised parents" could prove of interest in the context of graduate medical education. Einführung: "Standardisierte Patienten" (SP) sind simulierte Patienten, die sorgfältig und gewissenhaft trainiert wurden, um ihre erlernte Erkrankung in einer standardisierten und gleich bleibenden Art und Weise für didaktische Lehrzwecke zu präsentieren. SP werden in der Medizinischen Ausbildung zunehmend eingesetzt und sind inzwischen ein unverzichtbarer Bestandteil eines Kommunikationstrainings von Medizinstudenten. Auch für die Ausbildungscurricula von Assistenzärzten auf dem Weg zum Facharzt werden im angloamerikanischen Raum inzwischen SP eingesetzt. In der Pädiatrie wird die Verwendung von Schauspielern zu Schulungszwecken bisher nur vereinzelt beschrieben. Die wiederkehrende Frage nach einer ausreichenden Realitätsnähe und nach dem Nutzen ihres Feedbacks, wie sie bereits hinsichtlich des Einsatzes von SP aufgeworfen wurde, bleibt auch bei Schulungen mit "standardisierten Eltern", bei denen der Patient - das Kind - gar nicht oder nur teilweise anwesend ist, bestehen. Methode: In dem vorliegenden Projekt wurde für 28 Ärzte der Universitätsklinik für Kinder- und Jugendmedizin Heidelberg mit einer mittleren Berufserfahrung von 4,2 Jahren ein Kommunikationstraining mit "standardisierten Eltern" durchgeführt. Dazu wurden 13 Schauspieler anhand ausführlicher Rollenskripte für den Einsatz als "standardisierte Eltern" trainiert. Die Auswahl der Schauspieler erfolgte aus einem umfangreichen Pool an erfahrenen Schauspieler, die bereits Vorerfahrung im Einsatz als "standardisierte Patienten" hatten. Berufserfahrene pädiatrische Dienstärzte wurden anhand neun klinischer Szenarien im Umgang mit Problemen und schwierigen Gesprächssituationen im Kontakt mit Eltern erkrankter Kinder geschult. Im Anschluss an das Arzt-Eltern-Gespräch erhielten die trainierten Ärzte ein Feedback von den Schauspielern selbst, den teilnehmenden ärztlichen Kollegen ("peers") sowie den Supervisoren der Unterrichtsveranstaltungen. Mittels einer schriftlichen Evaluation der Teilnehmer wurde die Authentizität der "standardisierten Eltern" sowie die Relevanz der Fälle für eine praxisnahe Schulung hinsichtlich kommunikativer Fähigkeiten erfasst. Darüber hinaus wurde eine Einschätzung der Teilnehmer hinsichtlich der Qualität der nach dem Arzt-Eltern-Gespräch erhaltenen Feedbacks eingeholt. Ergebnis: Die Fälle der Schulungen wurden von den Ärzten als äußerst authentisch und relevant hinsichtlich der Verbesserung der eigenen kommunikativen Fertigkeiten und der Sicherheit im Umgang mit Eltern erkrankter Kinder gewertet. Die Teilnehmer bewerteten (sechsstufige Likert Skala:1 = trifft voll zu und 6 = trifft gar nicht zu ) das Feedback der Schauspieler (Mittelwert (M) = 1,08; Standardabweichung (SD) = 0,28), der Supervisoren (M = 1,25; SD = 0,68) und der "peers" (M =1,29; SD = 0,55) als etwa gleich relevant und nützlich. Diskussion: "Standardisierte Eltern" werden von angehenden Fachärzten der Pädiatrie als sehr authentisch eingeschätzt. Das Feedback der "standardisierten Eltern" wird als sehr hochwertig angesehen. Die Grundlage für diese Einschätzungen bildet eine fundierte Vorbereitung und Konzeption der Schulungsfälle sowie ein umfassendes Training der "standardisierten Eltern" hinsichtlich der Feedbackgabe. Ein weitreichender Einsatz von "standardisierten Eltern" wäre auch für die Ausbildung von angehenden Ärzten im Fachbereich Pädiatrie wünschenswert.

[english] "CAMPUS-Paediatrics" is an application of the computer-based learning system "CAMPUS" (http://www.medicase.de), with which authentic cases from the department of paediatric and juvenile medicine are presented in a realistic, interactive and multimedial way in order to test and improve the medical problem-solving competence of students. At the university clinic for paediatric and juvenile medicine in Heidelberg, this programme has been in use for five years within the context of tutorials and compulsory classes in small groups; the contents produced are relevant to examinations. The independent examination of the case on the computer in combination with dialogue and exchange of experiences with other students and the tutor in the sense of "blended learning" was judged in a number of evaluations by the students to be extremely effective. The project was/will be funded by the Ministry for Science and Art, Baden-Württemberg, the Federal Ministry for Education and Research and the Medical Faculty in Heidelberg. [german] "CAMPUS-Pädiatrie" ist eine Anwendung des computerbasierten Lernsystems "CAMPUS" (), mit dem authentische Fälle aus dem Fachbereich Kinder- und Jugendmedizin in einer realitätsnahen, interaktiven und multimedialen Weise bereitgestellt werden, um die medizinische Problemlösekompetenz von Studierenden zu testen und zu verbessern. An der Universitätsklinik für Kinder- und Jugendmedizin Heidelberg wird dieses Programm seit fünf Jahren im Rahmen des tutoriell betreuten und anwesenheitspflichtigen Kleingruppenunterrichts eingesetzt; die erarbeiteten Inhalte sind prüfungsrelevant. Die selbstständige Auseinandersetzung mit dem Lernfall am Computer in Kombination mit dem Gespräch und Erfahrungsaustausch mit anderen Studenten und dem Tutor im Sinne von "Blended Learning" wurde von den Studierenden in mehreren Evaluationen als sehr effektiv beurteilt. Das Projekt wurde bzw. wird vom MWK Baden-Württemberg, dem BMBF und der Medizinischen Fakultät Heidelberg gefördert.

In a search for the pathophysiologic mechanisms, we estimated isoprenoid synthesis and concentration, cellular growth, and the activity of the LDL receptor pathway in fibroblasts from patients with mevalonate kinase deficiency (MKD), a severe multisystemic disorder of cholesterol and non-sterol isoprenoid biosynthesis. In response to different concentrations of LDL and non-lipoprotein-bound cholesterol, MKD cells partially counteracted their enzyme defect by increased activities of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (results from earlier studies) and the LDL receptor pathway, responses similar to the pharmacologic effects seen upon administration of HMG-CoA reductase inhibitors. Rates of N-linked protein glycosylation, estimated as the amount of [14C]galactose-labeled macromolecules secreted into cell culture medium, were significantly decreased in MKD fibroblasts in comparison with control cells which may indicate alterations in the dolichol or dolichol phosphate pool. In response to exogenous cholesterol, the major feedback inhibitor of isoprenoid biosynthesis, growth velocities of MKD fibroblasts declined in comparison with control cells, further suggesting an impairment of non-sterol isoprenoid biosynthesis in MKD. Our results suggest an imbalance in the multilevel regulation of the biosynthesis of cholesterol and non-sterol isoprenoids in MKD, representing an additional causative factor responsible for the pre- and postnatal pathology of MKD.