Patientenkontakte im ersten Abschnitt der ärztlichen Ausbildung [Contact with patients in the preclinical term of medical education]

[english] The Department of Medical Sociology as part of the Medical Faculty of the University of Hamburg has developed a teaching concept focussing on doctor-patient-communication. Elements of the framework for implementing the concept are: 12 hours for the whole course, teaching has to be provided for 20 groups per year, continuous evaluation by students. Each student has to conduct an interview with an (ex-)patient on "patient's view of illness and health care". There is one teaching session about 4 hours for preparation, and another one for discussion of experiences with and results of the interviews. The concept takes into consideration the requirements both of the official curriculum for medical sociology and the new national regulations for physicans' examinations (Ärztliche Appprobationsordnung). In conclusion, a teaching model which is based on having the first experience of a structured patient interview is feasible for about 400 students in their first semester. The concept and in particular the interview are well accepted and positively evaluated by the students. In the last term, mean of overall satisfaction is about 5 on a 6-point agreement scale. The concept of the course in medical sociology (conducting a patient interview) can be applied in other universities. However, transferability depends on a time frame of about 0,75 hours per week during the semester. [german] Im Institut für Medizin-Soziologie der Medizinischen Fakultät Hamburg wurde ein Kurskonzept für das erste Semester entwickelt, das die Arzt-Patienten-Interaktion ins Zentrum stellt. Rahmenbedingungen für die Umsetzung sind: 0,8 Semesterwochenstunden (= ca. 12 Untersichtsstunden), 20 Kurs-Gruppen jährlich einmal im Wintersemester, kontinuierliche studentische Evaluationen. Als Kernelement des Kurses wird von jedem Studierenden ein Interview mit einem (Ex-)Patienten geführt. In je einem Zeitblock von ca. 4 Unterrichtsstunden wird das Interview vor- und nachbereitet. Als Hilfestellung dient ein Skript zum Thema des Kurses "Kranksein und Krankenbehandlung aus Patientensicht". Das Konzept berücksichtigt sowohl den Gegenstandskatalog der Medizinischen Soziologie als auch die Forderung der Approbationsordnung nach stärkeren klinischen Bezügen im Abschnitt Medizin 1. Als Schlussfolgerungen lassen sich festhalten: Ein Kursmodell für ca. 400 Studierende, in dessen Zentrum die erste Erfahrung eines strukturierten Gesprächs mit (Ex-)Patienten steht, ist machbar. Die Ergebnisse der studentischen Evaluation zeigen, dass der Kurs im Verlauf von vier Semestern zunehmend positiv bewertet wird. Im letzten Wintersemester 2005/2006 wird ein Wert von knapp 5 auf einer 6-stufigen Zustimmungsskala im Hinblick auf verschiedene Merkmale der Prozess- und Ergebnisqualität erreicht. Das Konzept ist mit Anpassungen an andere Rahmenbedingungen auch andernorts verwendbar

Inactivation of polycomb repressive complex 2 components in myeloproliferative and myelodysplastic/myeloproliferative neoplasms

The polycomb repressive complex 2 (PRC2) is a highly conserved histone H3 lysine 27 methyltransferase that regulates the expression of developmental genes. Inactivating mutations of the catalytic component of PRC2, EZH2, are seen in myeloid disorders. We reasoned that the other two core PRC2 components SUZ12 and EED may also bemutational targets in these diseases, as well as associated factors such as Jarid2. SUZ12 mutations were identified in 1 of 2 cases with myelodysplastic/myeloproliferative neoplasm (MDS/MPN) with 17q aUPD and 2 of 2 myelofibrosis cases with focal 17q11 deletions. All three were missense mutations affecting the highly conserved VEFS domain. Analysis of a further 146 MDS/MPN cases revealed an additional VEFS domain mutant, yielding a total mutation frequency of 2/148 (1.4%). We did not find mutations of Jarid2 or EED in association with aUPD for chromosome 6p or 11q, respectively, however screening unselected cases identified missense mutations in EED (1/148; 1%) and Jarid2 (3/148; 2%). All three SUZ12 mutations tested and the EED mutation reduced PRC2 histone methyltransferase activity in vitro, thus demonstrating that PRC2 function may be compromised in myeloid disorders by mutation of distinct genes

Gelatin-Modified Calcium/Strontium Hydrogen Phosphates Stimulate Bone Regeneration in Osteoblast/Osteoclast Co-Culture and in Osteoporotic Rat Femur Defects—In Vitro to In Vivo Translation

The development and characterization of biomaterials for bone replacement in case of large defects in preconditioned bone (e.g., osteoporosis) require close cooperation of various disciplines. Of particular interest are effects observed in vitro at the cellular level and their in vivo representation in animal experiments. In the present case, the material-based alteration of the ratio of osteoblasts to osteoclasts in vitro in the context of their co-cultivation was examined and showed equivalence to the material-based stimulation of bone regeneration in a bone defect of osteoporotic rats. Gelatin-modified calcium/strontium phosphates with a Ca:Sr ratio in their precipitation solutions of 5:5 and 3:7 caused a pro-osteogenic reaction on both levels in vitro and in vivo. Stimulation of osteoblasts and inhibition of osteoclast activity were proven during culture on materials with higher strontium content. The same material caused a decrease in osteoclast activity in vitro. In vivo, a positive effect of the material with increased strontium content was observed by immunohistochemistry, e.g., by significantly increased bone volume to tissue volume ratio, increased bone morphogenetic protein-2 (BMP2) expression, and significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio. In addition, material degradation and bone regeneration were examined after 6 weeks using stage scans with ToF-SIMS and µ-CT imaging. The remaining material in the defects and strontium signals, which originate from areas exceeding the defect area, indicate the incorporation of strontium ions into the surrounding mineralized tissue. Thus, the material inherent properties (release of biologically active ions, solubility and degradability, mechanical strength) directly influenced the cellular reaction in vitro and also bone regeneration in vivo. Based on this, in the future, materials might be synthesized and specifically adapted to patient-specific needs and their bone status

The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial

NOTCH1 and SF3B1 mutations have been previously reported to have prognostic significance in CLL but to datethey have not been validated in a prospective, controlled clinical trial. We have assessed the impact of thesemutations in a cohort of 494 patients treated within the randomized phase III UK LRF CLL4 trial that comparedchlorambucil and fludarabine with and without cyclophosphamide in previously untreated patients. Weinvestigated the relationship of mutations in NOTCH1 (exon 34) and SF3B1 (exon 14-16) to treatment response,survival and a panel of established biological variables. NOTCH1 and SF3B1 mutations were found in 10 and 17% ofpatients, respectively. NOTCH1 mutations correlated with unmutated IGHV genes, trisomy 12, high CD38/ ZAP-70expression and were associated with reduced overall (median 54.8 vs 74.6mths, P=0.02) and progression-free(median 22.0 vs. 26.4mths, P=0.02) survival. SF3B1 mutations were significantly associated with high CD38expression and with shorter overall survival (median 54.3 vs. 79.0mths, P<0.001). Furthermore, multivariateanalysis, including baseline clinical variables, treatment and adverse prognostic factors demonstrated that whileTP53 alterations remained the most informative marker of dismal survival in this cohort, NOTCH1 (HR 1.58, P=0.03)and SF3B1 (HR 1.52, P=0.01) mutations have added independent prognostic value