Non-vitamin K antagonist oral anticoagulants (NOACs) for thromboembolic prevention, are they safe in congenital heart disease? Results of a worldwide study.

BACKGROUND: Current guidelines consider vitamin K antagonists (VKA) the oral anticoagulant agents of choice in adults with atrial arrhythmias (AA) and moderate or complex forms of congenital heart disease, significant valvular lesions, or bioprosthetic valves, pending safety data on non-VKA oral anticoagulants (NOACs). Therefore, the international NOTE registry was initiated to assess safety, change in adherence and quality of life (QoL) associated with NOACs in adults with congenital heart disease (ACHD). METHODS: An international multicenter prospective study of NOACs in ACHD was established. Follow-up occurred at 6 months and yearly thereafter. Primary endpoints were thromboembolism and major bleeding. Secondary endpoints included minor bleeding, change in therapy adherence (≥80% medication refill rate, ≥6 out of 8 on Morisky-8 questionnaire) and QoL (SF-36 questionnaire). RESULTS: In total, 530 ACHD patients (mean age 47 SD 15 years; 55% male) with predominantly moderate or complex defects (85%), significant valvular lesions (46%) and/or bioprosthetic valves (11%) using NOACs (rivaroxaban 43%; apixaban 39%; dabigatran 12%; edoxaban 7%) were enrolled. The most common indication was AA (91%). Over a median follow-up of 1.0 [IQR 0.0-2.0] year, thromboembolic event rate was 1.0% [95%CI 0.4-2.0] (n = 6) per year, with 1.1% [95%CI 0.5-2.2] (n = 7) annualized rate of major bleeding and 6.3% [95%CI 4.5-8.5] (n = 37) annualized rate of minor bleeding. Adherence was sufficient during 2 years follow-up in 80-93% of patients. At 1-year follow-up, among the subset of previous VKA-users who completed the survey (n = 33), QoL improved in 6 out of 8 domains (p ≪ 0.05). CONCLUSIONS: Initial results from our worldwide prospective study suggest that NOACs are safe and may be effective for thromboembolic prevention in adults with heterogeneous forms of congenital heart disease.

A predictive model for alternative admission to dental education.

AIM: To compare academic progress and performance of students admitted through two admission systems and to analyse the predictive power of different components in an alternative admission. SAMPLE AND METHODS: The subjects were students admitted to the dental programme at Malmö University, Sweden. The grade admission group was admitted on grades from secondary school (n = 126) and the alternative admission group via an alternative admission procedure (n = 157). The alternative admission procedure consisted of the following components: problem-solving matrices, spatial capacity tested with folding and tin models, manual dexterity, capacity for empathy and interview. Comparisons were made for academic progress (dropouts from the programme and study rate) and academic performance (examinations failed and outcomes of a comprehensive clinical examination). Spearman correlation was calculated for each component of the alternative admission procedure and academic progress as well as academic performance. Multivariate analyses were also carried out. RESULTS: Compared to the grade admission group, the alternative admission group presented lower rate of dropouts (3% vs. 20%, P < 0.001) and a larger proportion graduated within the expected time (88% vs. 60%, P < 0.01). There was no difference between the groups concerning academic performance. Capacity of empathy was correlated with study rate and outcomes of the clinical examination. The matrices predicted low proportion failed examinations and high students' self-assessments in the clinical examination. Predictive power of folding was limited and so was that of the interview. Manual dexterity was not correlated with academic progress or performance. CONCLUSIONS: Results support further development of admission selection criteria, particularly emphatic capacity that predicts important student academic achievements.

D-dimer and risk of thromboembolic and bleeding events in patients with atrial fibrillation--observations from the ARISTOTLE trial.

BACKGROUND: D-dimer is related to adverse outcomes in arterial and venous thromboembolic diseases. OBJECTIVES: To evaluate the predictive value of D-dimer level for stroke, other cardiovascular events, and bleeds, in patients with atrial fibrillation (AF) treated with oral anticoagulation with apixaban or warfarin; and to evaluate the relationship between the D-dimer levels at baseline and the treatment effect of apixaban vs. warfarin. METHODS: In the ARISTOTLE trial, 18 201 patients with AF were randomized to apixaban or warfarin. D-dimer was analyzed in 14 878 patients at randomization. The cohort was separated into two groups; not receiving vitamin K antagonist (VKA) treatment and receiving VKA treatment at randomization. RESULTS: Higher D-dimer levels were associated with increased frequencies of stroke or systemic embolism (hazard ratio [HR] [Q4 vs. Q1] 1.72, 95% confidence interval [CI] 1.14-2.59, P = 0.003), death (HR [Q4 vs. Q1] 4.04, 95% CI 3.06-5.33) and major bleeding (HR [Q4 vs. Q1] 2.47, 95% CI 1.77-3.45, P < 0.0001) in the no-VKA group. Similar results were obtained in the on-VKA group. Adding D-dimer level to the CHADS2 score improved the C-index from 0.646 to 0.655 for stroke or systemic embolism, and from 0.598 to 0.662 for death, in the no-VKA group. D-dimer level improved the HAS-BLED score for prediction of major bleeds, with an increase in the C-index from 0.610 to 0.641. There were no significant interactions between efficacy and safety of study treatment and D-dimer level. CONCLUSION: In anticoagulated patients with AF, the level of D-dimer is related to the risk of stroke, death, and bleeding, and adds to the predictive value of clinical risk scores. The benefits of apixaban were consistent, regardless of the baseline D-dimer level.

Curriculum structure, content, learning and assessment in European undergraduate dental education - update 2010.

This paper presents an updated statement on behalf of the Association for Dental Education in Europe (ADEE) in relation to proposals for undergraduate Curriculum Structure, Content, Learning, Assessment and Student / Staff Exchange for dental education in Europe. A task force was constituted to consider these issues and the two previous, related publications produced by the Association (Plasschaert et al 2006 and 2007) were revised. The broad European dental community was circulated and contributed to the revisions. The paper was approved at the General Assembly of ADEE, held in Amsterdam in August 2010 and will be updated again in 2015.

Treatment with an oral direct thrombin inhibitor decreases platelet activity but increases markers of inflammation in patients with myocardial infarction.

BACKGROUND: Thrombin has a role not only in the coagulation process but also in inflammatory responses. Oral direct thrombin inhibitors (DTIs) are currently being evaluated in patients with thromboembolic diseases. OBJECTIVE: To investigate whether an oral DTI affects markers for platelet and inflammatory activity after myocardial infarction (MI). METHODS: A total of 518 patients with MI were randomly assigned to ximelagatran treatment (four different dose groups) in combination with aspirin, or aspirin alone for 6 months. The levels of soluble (s) P-selectin, soluble tissue factor, C-reactive protein (CRP), interleukin (IL)-10 and IL-18 were analysed in serial blood samples. RESULTS: sP-selectin concentration increased after 1 week and persisted at an elevated level for 6 months in all study groups (P < 0.001). In the two highest ximelagatran dose groups, there was a reduced increase in sP-selectin compared to treatment with lower doses of ximelagatran and aspirin alone (P = 0.01 and P = 0.002, respectively). IL-18 levels did not change in the aspirin alone treatment group. By contrast, there was an elevation in IL-18 level in the lower and higher ximelagatran dose groups after 6 months (P = 0.006 and P < 0.001, respectively). Ximelagatran increased IL-10 levels (P = 0.002) and reduced the decrease in CRP levels after 6 months compared to treatment with aspirin alone (P = 0.002). CONCLUSION: A persistent elevation of platelet activity is found in patients with a recent MI after the cessation of acute antithrombotic treatment, and the addition of an oral DTI at higher doses decreases the activity. By contrast, long-term treatment with a DTI increases the levels of several markers of inflammation. Further studies with prolonged exposure of oral DTIs are needed for evaluation of the effect on inflammatory processes and to determine whether these agents influence clinical outcomes.

Tissue factor and IL8 production by P-selectin-dependent platelet-monocyte aggregates in whole blood involves phosphorylation of Lyn and is inhibited by IL10.

BACKGROUND: P-selectin and CD40L expressed by activated platelets induce tissue factor (TF) and inflammatory cytokines in monocytes, but little is known of the cellular signaling pathways involved. The anti-inflammatory cytokine IL10 reduces atherosclerotic plaque formation. OBJECTIVES: To evaluate the importance of P-selectin upon platelet-monocyte aggregate (PMA) formation in thrombin receptor activator peptide (TRAP) stimulated whole blood, the P-selectin-P-selectin glycoprotein ligand (PSGL)-1-induced cellular signaling pathway, and the effects of IL10 on these functions. METHODS: TF, IL8, and monocyte chemotactic protein-1 (MCP-1) production, PMAs and phosphorylation of Lyn were analyzed in whole blood, purified monocytes, and vitamin D(3)-differentiated U-937 cells stimulated with TRAP or P-selectin with or without IL10. Anti-P-selectin or anti-CD40L antibodies (Abs), Src-kinases inhibitors, SU6656 or PP2, were added in some experiments. RESULTS: TRAP and P-selectin increased TF, IL8, and MCP-1 mRNA in whole blood and purified monocytes. Anti-P-selectin Ab reduced TRAP-induced PMA formation by 80 +/- 2% (P = 0.001) and production of TF (P = 0.04) and IL8 (P = 0.01). IL10 and SU6656 had no effect on PMA formation, although both significantly reduced TF (P = 0.002 and P = 0.02) and IL8 (P = 0.009 and P = 0.001) mRNA upon TRAP and P-selectin stimulation. Induced Lyn phosphorylation in monocytes was diminished by SU6656 (P = 0.02), anti-P-selectin Ab (P = 0.02), and IL10 (P = 0.03) upon TRAP or P-selectin stimulation. These results were confirmed in the vitamin D(3)-differentiated U-937 cells. CONCLUSIONS: The formation of PMAs in whole blood was P-selectin-dependent in the long term. P-selectin-PSGL-1-induced TF and IL8 expression through Lyn phosphorylation, and part of the inhibitory effect of IL10 depends on reduced phosphorylation.

Evaluation of student and faculty perceptions of the PBL curriculum at two dental schools from a student perspective: a cross-sectional survey.

Problem-based learning (PBL) research has primarily highlighted issues related to medical education and less evaluation has been reported from the field of dental education. Furthermore, literature reports tend to focus mainly on PBL from a pedagogic and curriculum constructional view and up to this date, studies from a student perspective are lacking. The aim of this study was to approach the evaluation of student and staff perceptions of PBL curricula from a student perspective at two separate schools: the Faculty of Odontology at the University of Malmö, Sweden and the dental school of the University of Southern California, School of Dentistry (USCSD), Los Angeles, CA, USA. The study was initiated and conducted by two of the authors, at the time senior students at the Faculty of Odontology in Malmö, Sweden. The study was comprised of a literature search, a 2 week field trip to USCSD, USA, survey distribution to students and faculty in both schools, analysis of the data and a written report for oral defence. The results from the survey were intended to provide feedback on student and faculty perceptions regarding the PBL curriculum. The results indicate a general student and faculty satisfaction with the PBL curriculum. Perhaps, surprisingly their perceptions did not differ significantly despite differences in geography, culture and implementation of PBL pedagogy.

Expression of HMGB1 during tooth development.

High mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that can act as a transcription factor, a growth factor, or a cytokine. To elucidate a possible role for HMGB1 in tooth development, we have studied the expression of HMGB1 and its receptor RAGE (receptor for advanced glycation end-products) during the late fetal and early postnatal period of rat by using light- and electron-microscopic immunohistochemistry. Low HMGB1 protein expression was observed during fetal and newborn stages of tooth development. However, from postnatal day 5 (P5) onward, a marked increase occurred in the levels of the protein in most dental cell types. Expression was particularly high in ameloblasts and odontoblasts at regions of ongoing mineralization. Although most HMGB1 immunoreactivity was confined to cell nuclei, it was also present in odontoblast cytoplasm. At P5, ameloblasts and odontoblasts also showed RAGE immunoreactivity, and reverse transcription-polymerase chain reaction demonstrated both HMGB1 and RAGE mRNA in human dental pulp cells in vitro. Immunoblots performed on extracts from bovine dentin demonstrated a principal band at approximately 27 kDa, indicating that HMGB1 participates in tooth mineralization. The expression of both ligand and receptor suggests an autocrine/paracrine HMGB1 signalling axis in odontoblasts.

Long-term treatment with ximelagatran, an oral direct thrombin inhibitor, persistently reduces the coagulation activity after a myocardial infarction.

BACKGROUND: In the ESTEEM study, patients with a recent myocardial infarction were treated with aspirin and randomized to one of four doses (24-60 mg b.i.d) of the oral direct thrombin inhibitor ximelagatran or placebo for 6 months. Ximelagatran and aspirin reduced the risk of recurrent ischemic events compared with aspirin alone. In the present substudy we evaluated the different doses of ximelagatran on pharmacokinetics as measured by plasma concentration of the active compound melagatran and activated partial thromboplastin time (APTT) and pharmacodynamics as related by markers for coagulation activity, prothrombin fragment 1 + 2 (F1 + 2) and D-dimer. METHODS AND RESULTS: Plasma samples from 518 patients were collected before, during and after the treatment period. There was a linear dose-concentration relation at peak and trough and a linear relation between concentration and APTT (P < 0.001). F1 + 2 and D-dimer were decreased by 25% and 52% at 1 week (P < 0.001) in the ximelagatran groups compared with the placebo group and the reductions were maintained during the 6 months treatment. There were no differences detected in F1 + 2 or D-dimer levels between the different ximelagatran dosages. There was no correlation between the melagatran concentration and the change in F1 + 2 and D-dimer levels. After cessation of ximelagatran F1 + 2 and D-dimer levels returned to the initial levels. CONCLUSION: The dose of ximelagatran and APTT are linearly related to the plasma concentration of melagatran. Ximelagatran induces a sustained and stable reduction of thrombin generation and fibrin turnover without any relation to dose above 24 mg b.i.d. These properties indicate that long-term treatment with a low dose of ximelagatran may provide valuable depression of coagulation activity in aspirin treated post myocardial infarction patients.

Rat enamel contains RP59: a new context for a protein from osteogenic and haematopoietic precursor cells.

We have recently identified a protein, RP59, in bone marrow cells and young osteoblasts, in cells involved in bone repair and in young erythroblasts and megakaryocytes. Here, we report immunohistochemical data at the light- and electron-microscope level indicating that RP59 is also present in newly secreted tooth enamel of the rat and in ameloblasts, the formative cells. In enamel matrix, RP59 was located proximal to secretory ameloblasts only, i.e. in newly secreted material. Distal enamel and enamel in association with maturation stage ameloblasts were unlabelled. Secretory ameloblasts contained RP59 in the matrix-proximal region including Tomes' processes, post-secretory ameloblasts in the cell-matrix interface. Western blotting of proteins from tooth germs identified RP59 as a band at 90 kD, co-migrating with RP59 from bone marrow and spleen. Antisera versus a chemically synthesised RP59 peptide and versus a bacteria-synthesised protein fragment reacted in the same manner. In situ hybridisation of tooth tissue revealed RP59 RNA specifically in ameloblasts. The reverse transcription/polymerase chain reaction method identified tooth RNA coding for RP59. Sequence analysis indicated that RP59 RNA from tooth and marrow had the same sequence. An internal sequence motif was found in rat RP59 resembling a signal implicated in secretion of the chicken "engrailed" gene product. The findings indicate that RP59 is a genuine product of ameloblasts and that it is secreted in the course of enamel formation together with other matrix components.

Characterisation of structures in salivary secretion film formation. An experimental study with atomic force microscopy.

The purpose of the present study was to characterise the structure dynamics of pure salivary secretions retained on controlled surfaces with different surface energies in the early stage of salivary film formation. Germanium prisms prepared to have either low surface energy or medium surface energy were incubated in fresh secretions of either human parotid saliva (HPS) or human submandibular/sublingual saliva (HSMSLS) for 15, 90, and 180 min. After controlled rinsing with distilled water, the surfaces were air dried and thereafter imaged with atomic force microscopy (AFM). The amount of adsorbed material and the size of the structures detected increased with increased saliva exposure time. The film thicknesses varied from 10 to 150 nm, and both HPS and HSMSLS films contained structures with diameters varying from 40 nm to 2 microm. Some of these were clustered into special formations. The HPS films exhibited a more granular morphology than the HSMSLS films. Furthermore, branched lines were detected on the low surface energy germanium prisms incubated in saliva. The results indicate that exposure time, surface energy, and type of salivary secretion all are factors affecting the adsorption characteristics of salivary films.

A new protein expressed in bone marrow cells and osteoblasts with implication in osteoblast recruitment.

To study osteoblast recruitment from bone marrow cells, a rat femur cDNA library was screened by in situ hybridization for novel mRNA sequences that are frequently expressed in both marrow cells and osteoblasts. One isolated clone, called RP59, is described here. Northern blots indicated two bands of 2.6 and 2.8 kb in femur and spleen, tissues containing high amounts of immature mesenchymal cells, and no or little expression in other tissues. The cDNA sequence revealed a reading frame for a repetitive protein composed of arrays of 14-mers and phased phosphorylation sites. Antisera versus RP59 detected a single band of 90 kDa by Western blotting of femur extract. Immunohistochemistry indicated strong RP59 presence in the cytoplasm of bone marrow cells and weaker presence in nuclei of osteoblasts. Intermediate stages were found between strongly labeled, round, free bone marrow cells and weaker labeled, fibroblast-like young osteoblasts associated with bone matrix. These data indicated that marrow cells with high RP59 content were recruited into growing bone tissue. RP59 may help to study the transition of bone marrow cell to osteoblast in more detail.

Macromolecular organization of saliva: identification of 'insoluble' MUC5B assemblies and non-mucin proteins in the gel phase.

Stimulated human submandibular/sublingual (HSMSL) and whole saliva were separated into sol and gel phases and mucins were isolated by density-gradient centrifugation in CsCl/4M guanidinium chloride. MUC5B and MUC7 were identified using anti-peptide antisera raised against sequences within the MUC5B and MUC7 apoproteins respectively. MUC7 was found mainly in the sol phase of both HSMSL and whole saliva, but some MUC7 was consistently present in the gel phase, suggesting that this mucin may interact with the salivary gel matrix. In HSMSL saliva, MUC5B was found in the gel phase; however, most of the material was 'insoluble' in guanidinium chloride and was only brought into solution by reduction. In whole saliva, the MUC5B mucin was present both in the sol and gel phases although some material was again 'insoluble'. Rate-zonal centrifugation of whole saliva showed that MUC5B mucins in the sol phase were smaller than those in the gel phase, suggesting differences in oligomerization and/or degradation. Antibodies against IgA, secretory component, lysozyme and lactoferrin were used to study the distribution of non-gel-forming proteins in the different phases of saliva. The majority of these proteins was found in the sol phase of both HSMSL and whole saliva. However, a significant fraction was present in the gel phase of whole saliva, suggesting a post-secretory interaction with the salivary gel matrix. A monoclonal antibody against a parotid salivary agglutinin was used to show that this protein is present mainly in the gel phase of both whole saliva and parotid secretion.

Film-forming properties and viscosities of saliva substitutes and human whole saliva.

Hypo-salivation, related to medical remedies, is an increasing clinical problem. Studies report a weak correlation between subjective mouth dryness and objective sialometry. This indicates that both quantity and quality of saliva are important for the surface-associated functions of saliva, such as lubrication and hydration, to be expressed. Film-forming properties and viscosities of three saliva substitutes were compared to human saliva. Adsorption to surfaces was measured by ellipsometry, infrared spectroscopy and drop-volume technique. Viscosity measurements were carried out using an oscillating rheometer. Saliva, with the lowest viscosity value and the highest protein content, presented superior film retention on both hydrophilic and hydrophobic surfaces. The carboxymethylcellulose-based MAS 84 showed intermediate values of viscosity, poorest ability to reduce surface tension, and negligible film-forming capacity. The porcine mucin-based Saliva Orthana showed about twice the viscosity of saliva and film-forming capability on preferably hydrophobic substrates. Salinum, a linseed extract, possessed the highest viscosity value and an initial surface tension close to that of saliva. The film retention on hydrophilic surfaces was not as effective as for saliva. The results indicate that the film-forming capacity of saliva substitutes is a property also to be considered in the exploration of clinically effective artificial salivas.

Endochondral bone formation in toothless (osteopetrotic) rats: failures of chondrocyte patterning and type X collagen expression.

The pacemaker of endochondral bone growth is cell division and hypertrophy of chondrocytes. The developmental stages of chondrocytes, characterized by the expression of collagen types II and X, are arranged in arrays across the growth zone. Mutations in collagen II and X genes as well as the absence of their gene products lead to different, altered patterns of chondrocyte stages which remain aligned across the growth plate (GP). Here we analyze GP of rats bearing the mutation toothless (tl) which, apart from bone defects, develop a progressive, severe chondrodystrophy during postnatal weeks 3 to 6. Mutant GP exhibited disorganized, non-aligned chondrocytes and mineralized metaphyseal bone but without cartilage mineralization or cartilaginous extensions into the metaphysis. Expression of mRNA coding for collagen types II (Col II) and X (Col X) was examined in the tibial GP by in situ hybridization. Mutant rats at 2 weeks exhibited Col II RNA expression and some hypertrophied chondrocytes (HC) but no Col X RNA was detected. By 3rd week, HC had largely disappeared from the central part of the mutant GP and Col II RNA expression was present but weak and in 2 separate bands. Peripherally the GP contained HC but without Col X RNA expression. This abnormal pattern was exacerbated by the fourth week. Bone mineralized but cartilage in the GP did not. These data suggest that the tl mutation involves a regulatory function for chondrocyte maturation, including Col X RNA synthesis and mineralization, and that the GP abnormalities are related to the Col X deficiency. The differences in patterning in the tl rat GP compared to direct Col X mutations may be explained by compensatory effects.

Expression of collagen alpha1(I) mRNA variants during tooth and bone formation in the rat.

Collagen alpha1(I) mRNA is composed of two variants of 5 and 6 kb, differing in the length of the 3' untranslated region. In this work, the nucleotide sequences of the two rat mRNA variants were compared, and their expression pattern in cells forming bone, dentin, and cementum were analyzed. The sequences were determined from cDNA inserts of tooth and bone libraries plus directly from PCR fragments, obtained from bone. A total of 5721 bases of the rat collagen alpha1(I) sequence from cDNA of tooth and bone was determined. All sequences of the short variant were represented in the long variant. Only the alternatively poly-A additions gave rise to the variants in hard tissue. Two oligonucleotides were chosen as probes, one of which recognized, on Northern blots, the two bands of 5 and 6 kb, and the other the 6-kb variant only. The oligonucleotides were used in in situ hybridization experiments, for study of the distribution of the variants in different extracellular matrix-forming cells. Osteoblasts, odontoblasts, and cementum-associated cells were closely examined in sections from rat maxillae from 2 to 25 days of age. A similar or identical pattern of mRNA expression was observed with both oligonucleotides, indicating that the two mRNA variants were co-expressed in all cases.

Collagen mRNA expression during tissue development: the temporospacial order coordinates bone morphogenesis with collagen fiber formation.

Bone formation of the maxilla and premaxilla of rats was studied by in situ hybridization, using probes for fibrillar collagen mRNAs. Chondroblasts, osteoblasts, fibroblasts and peripheral bone cells differed in their expression patterns. Prospective nasal chondroblasts expressed collagen alpha1(II) and alpha1(XI) RNA from day 15 post coitum. Bone formation in the adjacent maxilla and premaxilla started around day 17: groups of osteoblasts, representing ossification centers, expressed collagen alpha1(I) RNA strongly, and alpha1(V), alpha2(V) and alpha1(XI) RNA weakly, but they were deficient in collagen alpha1(III) RNA. As the centers expanded, osteoblasts in the resulting bone domains expressed collagen alpha1(I) RNA in abundance, whereas collagen alpha1(III) RNA was absent. Bone domains were surrounded by fibroblasts containing collagens alpha1(I), alpha1(III) and alpha2(V) RNA. Widely separated fibroblasts underwent condensation into densely packed periosteum and sutural soft tissues. Cells at the periphery of fast-growing bone domains also displayed, apart from collagen alpha1(I) RNA, collagens alpha2(V) and alpha1(XI) RNA. Given the continuous recruitment of cells from the periosteum, peripheral bone cells represent differentiating osteoblasts synthetizing collagens alpha2(V) and alpha1 (XI) RNA transiently. Thus, gene expression during osteoblast differentiation reflects synthesis of fiber components during bone growth, since collagen V is located in the center of fibers consisting primarily of collagen I.

Osteonectin RNA and collagen alpha1(I) RNA in the developing rat maxilla.

The sequence of rat osteonectin mRNA was determined. Comparison with osteonectin (ON) mRNA sequences of other vertebrates showed a great similarity, but a stretch of codons deviated with respect to another rat strain, suggesting the possibility of two ON variants in rats. Northern blots exhibited one band of ON mRNA only. The expression of ON and collagen alpha1(I) RNA in tissues of the developing rat maxilla was studied by in situ hybridization. Both ON and collagen alpha1(I) RNA were observed concomitantly in osteoblasts, starting from the onset of bone formation at day 17 post coitum through the oldest age examined, day 20 after birth. A strict co-expression of the two sequences was also observed in odontoblasts as well as in fibroblasts of the periodontal ligament. In ameloblasts, neither ON nor collagen alpha1(I) RNA was detected under stringent hybridization conditions, but lower stringency led to an ON signal. Considering that ON is a secretory protein and the high stability of the ON mRNA, the co-expression of collagen alpha1(I) and ON RNA sequences in matrix-forming cells provided evidence that ON is a substantial component of collagen matrices.

Clinical guidelines and self-assessment in dental education.

This paper describes an educational programme where clinical guidelines are used in dental education and assesses the value of these guidelines as perceived by undergraduate students. It presents a comparison of students' own assessments of their performance with those of their instructors, according to such guidelines. The educational programme at the Faculty of Odontology, Lund University, is described through 3 main principles: problem-based learning, adoption of a holistic attitude to patient care and the promotion of oral health. The dental curriculum occupies 5 years comprising 10 semesters. 41, 5th semester students (16 male and 25 female) participated in the study. Students were introduced to guidelines in group discussions at the beginning of the semester. At the completion of a patient's planned course of treatment, the outcome was formally assessed both by students and clinical instructors. Performance was scored in various categories as "excellent", "acceptable" or "unacceptable" according to the standards defined. A total of 1373 scores were made by both students and instructors. 88% cent of students used the guidelines often or almost always and found them useful. Overall, no students received an "unacceptable" score and 40% of students achieved a score of "excellent". Female students tended towards a higher score, but this was not significant. Instructors' and students' scores agreed in almost 90% of instances. Students under-scored their performance more frequently than they over-scored it. It appears that the use of clinical guidelines may encourage an increased awareness of the decision-making processes involved in clinical practice, but it must be acknowledged that these guidelines are complex both in derivation and application.