Multiple adenosine 3',5'-cyclic [corrected] monophosphate response element DNA-binding proteins generated by gene diversification and alternative exon splicing.

The protein sequence deduced from the open reading frame of a human placental cDNA encoding a cAMP-responsive enhancer (CRE)-binding protein (CREB-327) has structural features characteristic of several other transcriptional transactivator proteins including jun, fos, C/EBP, myc, and CRE-BP1. Results of Southwestern analysis of nuclear extracts from several different cell lines show that there are multiple CRE-binding proteins, which vary in size in cell lines derived from different tissues and animal species. To examine the molecular diversity of CREB-327 and related proteins at the nucleic acid level, we used labeled cDNAs from human placenta that encode two different CRE-binding proteins (CREB-327 and CRE-BP1) to probe Northern and Southern blots. Both probes hybridized to multiple fragments on Southern blots of genomic DNA from various species. Alternatively, when a human placental c-jun probe was hybridized to the same blot, a single fragment was detected in most cases, consistent with the intronless nature of the human c-jun gene. The CREB-327 probe hybridized to multiple mRNAs, derived from human placenta, ranging in size from 2-9 kilobases. In contrast, the CRE-BP1 probe identified a single 4-kilobase mRNA. Sequence analyses of several overlapping human genomic cosmid clones containing CREB-327 sequences in conjunction with polymerase chain reaction indicates that the CREB-327/341 cDNAs are composed of at least eight or nine exons, and analyses of human placental cDNAs provide direct evidence for at least one alternatively spliced exon. Analyses of mouse/hamster-human hybridoma DNAs by Southern blotting and polymerase chain reaction localizes the CREB-327/341 gene to human chromosome 2. The results indicate that there is a dichotomy of CREB-like proteins, those that are related by overall structure and DNA-binding specificity as well as those that are related by close similarities of primary sequences.

The European Board of Physical and Rehabilitation Medicine : the past, the present and the future [Europejska Rada Medycyny Fizykalnej i Rehabilitacji: przeszłość, teraźniejszość i perspektywy]

Right from the beginning of the development of the medical specialty of Physical and Rehabilitation Medicine (PRM) the harmonization of the fields of competence and the specialist training across Europe was always an important issue. The initially informal European collaboration was formalized in 1963 under the umbrella of the European Federation of PRM. The European Academy of PRM and the UEMS section of PRM started to contribute in 1969 and 1974 respectively. In 1991 the European Board of Physical and Rehabilitation Medicine (EBPRM) was founded with the specific task of harmonizing education and training in PRM in Europe. The EBPRM has progressively defined curricula for the teaching of medical students and for the postgraduate education and training of PRM specialists. It also created a harmonized European certification system for medical PRM specialists, PRM trainers and PRM training sites. European teaching initiatives for PRM trainees (European PRM Schools) were promoted and learning material for PRM trainees and PRM specialists (e-learning, books and e-books, etc.) was created. For the future the Board will have to ensure that a minimal specific undergraduate curriculum on PRM based on a detailed European catalogue of learning objectives will be taught in all medical schools in Europe as a basis for the general medical practice. To stimulate the harmonization of national curricula, the existing postgraduate curriculum will be expanded by a syllabus of competencies related to PRM and a catalogue of learning objectives to be reached by all European PRM trainees. The integration of the certifying examination of the PRM Board into the national assessment procedures for PRM specialists will also have to be promoted.

Iron and transfusion medicine.

Blood bankers have focused their energy to secure blood transfusion, and only recently have studies been published on the effect of blood donation on iron metabolism. In many facilities, hemoglobin measurement is only performed just before or even during blood donation, but the determination of iron stores is largely ignored. The 2013 paradox of transfusion medicine is due to the fact that blood donation may be harmful and leads to iron deficiency with or without anemia, but for other individuals, it may be a healthy measure preventing type 2 diabetes. The purpose of this review is to discuss iron metabolism in the perspective of blood donation, notably regarding their possible genetic profiles that eventually will discriminate "good" iron absorbers from "bad" iron responders.

CNVs and genetic medicine (excitement and consequences of a rediscovery).

The extensive variability of individual human genomes contributes to phenotypic variability. Structural genomic variants, and copy number variants (CNVs) in particular, have recently been rediscovered as contributors to the genomic plasticity and evolution and as pathoetiologic elements for both monogenic and complex traits. Herein we review some of the consequences of CNVs in the context of human inherited diseases.

Cell-derived microparticles in haemostasis and vascular medicine.

Considerable interest for cell-derived microparticles has emerged, pointing out their essential role in haemostatic response and their potential as disease markers, but also their implication in a wide range of physiological and pathological processes. They derive from different cell types including platelets - the main source of microparticles - but also from red blood cells, leukocytes and endothelial cells, and they circulate in blood. Despite difficulties encountered in analyzing them and disparities of results obtained with a wide range of methods, microparticle generation processes are now better understood. However, a generally admitted definition of microparticles is currently lacking. For all these reasons we decided to review the literature regarding microparticles in their widest definition, including ectosomes and exosomes, and to focus mainly on their role in haemostasis and vascular medicine.

Body, Disease and Treatment in a Changing World. Latin texts and contexts in ancient and medieval medicine (Proceedings of the ninth International Conference «Ancient Latin Medical Texts», Hulme Hall, University of Manchester, 5th-8th September 2007),

This volume reflects a variegated and fruitful dialogue between classical and medieval philologists and historians of science, philosophy, literature and language as well as of medicine - the diverse range of interests that the history of medicine in the Graeco-Roman world and the medieval West continues to stimulate and draw on. A recurrent theme is the transformation of medical knowledge in different languages, literary forms and cultural milieux. Several papers concern editorial work in progress on unpublished texts, available only in manuscript or early printed editions. Ce recueil met en dialogue des spécialistes des textes médicaux latins de l'Antiquité et du Moyen Âge. Certaines analyses adoptent une approche sociolinguistique, d'autres s'intéressent à des questions de transmission et de réception, d'autres enfin livrent des études sur le lexique médical. Mais toutes concourent à éclairer une histoire culturelle de la médecine qui s'inscrit dans un monde en mutation. With a preface by D. R. Langslow, and contributions by M. Baldin, J. P. Barragán Nieto, P. P. Conde Parrado, D. Crismani, M. Cronier, C. de la Rosa Cubo, A. Ferraces Rodríguez, K.-D. Fischer, P. Gaillard-Seux, A. García González, V. Gitton-Ripoll, G. Haverling, F. Le Blay, B. Maire, G. Marasco, A. I. Martín Ferreira, I. Mazzini, F. Messina, Ph. Mudry, V. Nutton, M. Pardon-Labonnelie, R. Passarella, M. J. Pérez Ibáñez, S. Sconocchia, A. M. Urso, M. E. Vázquez Buján, and H. von Staden.

Thérapeutique et médecine interne générale [Therapy and internal medicine].

This review is based on five articles published in 2006 and dealing with therapies in general internal medicine: in case of acute non complicated rhino-sinusitis, the use of topical corticoids in mono-therapy is indicated; cross-reactivity between penicillins and cephalosporins is less frequent than established so far. In our daily practice we should be more "pro-active" in prescribing probiotics which have proved their efficacy in the prevention of antibiotic-associated diarrhoeas; an antibiotic treatment of three days is recommended in case of non complicated cystitis in women less than 65 years of age. Finally, every patient treated with bisphosphonates must be regularly followed by a dentist.

Lésions buccales du reflux gastro-oesophagien de l'enfant: des réalités et quelques mythes [An interface between pediatrics and oral medicine: oral manifestations of gastroesophageal reflux in children]

Gastro-oesophageal reflux (GOR) is a common disorder in the pediatric population. In association with esophagitis, GOR may impair children's quality of life. Extra-oesophageal manifestations are of specific interest in oral medicine because the refluxate may reach impair both oral mucosa and hard dental tissues. Some oral symptoms are so specific that they should raise the attention for other GOR symptoms. Dental erosion is a potential risk in children with gastroesophageal reflux: the pediatrician should routinely refer children with gastroesophageal reflux to a pediatric dentist to diagnose erosions and if needed restore the teeth. Conversely, in the presence of unexplained dental erosions the dentist and/or the pediatrician should discuss the possibility of an occult GOR.

Harmonization of training and assessment of medical specialists in physical and rehabilitation medicine across Europe - The contribution of the UEMS Board of Physical and Rehabilitation Medicine

Background.- The main goals of the European Board of Physical and Rehabili-tation Medicine (EBPRM), founded in 1991 as the third speciality board of theUnion of European Medical Specialists (UEMS), are to harmonize pre-graduate,post-graduate and continuous medical education in physical and rehabilitationmedicine (PRM) all over Europe. The harmonization of curricula of the medi-cal specialities and the assessment of medical specialists has become one of thepriorities of the UEMS and its working groups to which the EBPRM contributes.Action.- The EBPRM will continue to promote a specific minimal undergraduatecurriculum on PRM including issues like disability, participation and handicapto be taught all over Europe as a basis for general medical practice. The EBPRMwill also expand the existing EBPRM postgraduate curriculum into a detailedcatalogue of learning objectives. This catalogue will serve as a tool to boostharmonization of the national curricula across Europe as well as to structurethe content of the MCQ examination. It would be a big step forward towardsharmonization of European PRM specialist training if an important number ofcountries would use the certifying MCQ examination of the Board as a part ofthe national assessments for PRM specialists.

Educational resources offered by the European Board of Physical and Rehabilitation Medicine (EBPRM)

Background .- Physical and Rehabilitation Medicine (PRM) is a very demanding medical speciality. To ensure high standard of research and care in PRM all across Europe, it is crucial to attract gifted trainees and offer them high quality education. At undergraduate level, many medical schools in Europe omit to offer teaching on disabled persons and on basic PRM knowledge. Thus PRM is hardly known to medical students. For postgraduate trainees access to evidence-based knowledge as well as teaching of research methodology specific to PRM, rehabilitation methodology, disability management and team building also need to be strengthened to increase the visibility of PRM. Action .- To address these issues the EBPRM proposes presently a specific undergraduate curriculum in PRM including the issues of disability, participation and handicap as a basis for general medical practice and postgraduate rehabilitation training. For PRM trainees many educational documents are now available on the EBPRM website. A growing number of educational sessions for PRM trainees take place during international and national PRM Congresses which can be accessed at low cost. Educational papers published regularly in European rehabilitation journals and European PRM Schools are offered free or at very low cost to trainees.

Metastatic tumors to the colon and rectum: a multi-institutional study.

Context.-Unlike the small bowel, the colorectal mucosa is seldom the site of metastatic disease. Objective.-To determine the incidence of truly colorectal metastases, and subsequent clinicopathologic findings, in a substantial colorectal cancer population collected from 7 European centers. Design.-During the last decade, 10 365 patients were identified as having colorectal malignant tumors, other than systemic diseases. Data collected included patient demographics, clinical symptoms, treatment, the presence of metastases in other sites, disease-free interval, follow-up, and overall survival. All secondary tumors resulting from direct invasion from malignant tumors of the contiguous organs were excluded, as well as those resulting from lymph node metastases or peritoneal seeding. Results.-Only 35 patients were included (10 men) with a median age of 59 years. They presented with obstruction, bleeding, abdominal pain, or perforation. The leading source of metastases was the breast, followed by melanoma. Metastases were synchronous in 3 cases. The mean disease-free interval for the remaining cases was 6.61 years. Surgical resection was performed in 28 cases. Follow-up was available for 26 patients; all had died, with a mean survival time of 10.67 months (range, 1-41 months). Conclusions.-Colorectal metastases are exceptional (0.338%) with the breast as a leading source of metastases; they still represent a late stage of disease and reflect a poor prognosis. Therefore, the pathologist should be alert for the possibility of secondary tumors when studying large bowel biopsies. Any therapy is usually palliative, but our results suggest that prolonged survival after surgery and complementary therapy can be obtained in some patients.

Cerebrospinal fluid PCR analysis and biochemistry in bodies with severe decomposition.

The aim of this study was to assess whether Neisseria meningitidis, Listeria monocytogenes, Streptococcus pneumoniae and Haemophilus influenzae can be identified using the polymerase chain reaction technique in the cerebrospinal fluid of severely decomposed bodies with known, noninfectious causes of death or whether postmortem changes can lead to false positive results and thus erroneous diagnostic information. Biochemical investigations, postmortem bacteriology and real-time polymerase chain reaction analysis in cerebrospinal fluid were performed in a series of medico-legal autopsies that included noninfectious causes of death with decomposition, bacterial meningitis without decomposition, bacterial meningitis with decomposition, low respiratory tract infections with decomposition and abdominal infections with decomposition. In noninfectious causes of death with decomposition, postmortem investigations failed to reveal results consistent with generalized inflammation or bacterial infections at the time of death. Real-time polymerase chain reaction analysis in cerebrospinal fluid did not identify the studied bacteria in any of these cases. The results of this study highlight the usefulness of molecular approaches in bacteriology as well as the use of alternative biological samples in postmortem biochemistry in order to obtain suitable information even in corpses with severe decompositional changes.