A multidisciplinary approach to the functional and esthetic rehabilitation of amelogenesis imperfecta and open bite deformity: a case report

The treatment of amelogenesis imperfecta (AI) with an anterior open bite (AOB) is a challenge for the clinician and often requires a multidisciplinary team of specialists. Most often, patients suffering from these conditions are young and a good functional and esthetic long-term result must be aspired. This clinical report illustrates the orthodontic, maxillofacial, restorative, and prosthodontic rehabilitation of a 20-year-old woman with a hypoplastic form of AI and an AOB malocclusion, having received treatment for the last 6 years. It included adhesive resin composite restorations, orthodontical and maxillofacial surgery with a one-piece Le Fort I osteotomy, and a genioplasty. Subsequent prosthodontic therapy consisted of 28 all-ceramic crowns whereby a solid interdigitation, a canine guidance, and consistent and regular contacts between tooth crowns could be achieved to assure a good functional and esthetic oral situation. The tooth preparation techniques guaranteed minimally invasive treatment. The patient was affected very positively. CLINICAL SIGNIFICANCE: This article describes an interdisciplinary approach to the successful treatment of a patient with a hypoplastic form of amelogenesis imperfecta over a period of 6 years. It starts with a discussion of the conservative steps taken during adolescence and concludes with the final prosthetic rehabilitation with all-ceramic crowns after reaching adulthood.

Mapping of a new locus for congenital anomalies of the kidney and urinary tract on chromosome 8q24

Congenital anomalies of the kidney and urinary tract (CAKUT) account for the majority of end-stage renal disease in children (50%). Previous studies have mapped autosomal dominant loci for CAKUT. We here report a genome-wide search for linkage in a large pedigree of Somalian descent containing eight affected individuals with a non-syndromic form of CAKUT.

Interaction of the receptor FGFRL1 with the negative regulator Spred1

FGFRL1 is a member of the fibroblast growth factor receptor family. It plays an essential role during branching morphogenesis of the metanephric kidneys, as mice with a targeted deletion of the Fgfrl1 gene show severe kidney dysplasia. Here we used the yeast two-hybrid system to demonstrate that FGFRL1 binds with its C-terminal, histidine-rich domain to Spred1 and to other proteins of the Sprouty/Spred family. Members of this family are known to act as negative regulators of the Ras/Raf/Erk signaling pathway. Truncation experiments further showed that FGFRL1 interacts with the SPR domain of Spred1, a domain that is shared by all members of the Sprouty/Spred family. The interaction could be verified by coprecipitation of the interaction partners from solution and by codistribution at the cell membrane of COS1 and HEK293 cells. Interestingly, Spred1 increased the retention time of FGFRL1 at the plasma membrane where the receptor might interact with ligands. FGFRL1 and members of the Sprouty/Spred family belong to the FGF synexpression group, which also includes FGF3, FGF8, Sef and Isthmin. It is conceivable that FGFRL1, Sef and some Sprouty/Spred proteins work in concert to control growth factor signaling during branching morphogenesis of the kidneys and other organs.

Malignant melanoma and bone resorption

The cellular and humoral mechanisms accounting for osteolysis in skeletal metastases of malignant melanoma are uncertain. Osteoclasts, the specialised multinucleated cells that carry out bone resorption, are derived from monocyte/macrophage precursors. We isolated tumour-associated macrophages (TAMs) from metastatic (lymph node/skin) melanomas and cultured them in the presence and absence of osteoclastogenic cytokines and growth factors. The effect of tumour-derived fibroblasts and melanoma cells on osteoclast formation and resorption was also analysed. Melanoma TAMs (CD14+/CD51-) differentiated into osteoclasts (CD14-/CD51+) in the presence of receptor activator for nuclear factor kappaB ligand (RANKL) and macrophage-colony stimulating factor. Tumour-associated macrophage-osteoclast differentiation also occurred via a RANKL-independent pathway when TAMs were cultured with tumour necrosis factor-alpha and interleukin (IL)-1alpha. RT-PCR showed that fibroblasts isolated from metastatic melanomas expressed RANKL messenger RNA and the conditioned medium of cultured melanoma fibroblasts was found to be capable of inducing osteoclast formation in the absence of RANKL; this effect was inhibited by the addition of osteoprotegerin (OPG). We also found that cultured human SK-Mel-29 melanoma cells produce a soluble factor that induces osteoclast differentiation; this effect was not inhibited by OPG. Our findings indicate that TAMs in metastatic melanomas can differentiate into osteoclasts and that melanoma fibroblasts and melanoma tumour cells can induce osteoclast formation by RANKL-dependent and RANKL-independent mechanisms, respectively.

Prediction of first coronary events with the Framingham score: a systematic review

BACKGROUND: Uncertainty exists about the performance of the Framingham risk score when applied in different populations. OBJECTIVE: We assessed calibration of the Framingham risk score (ie, relationship between predicted and observed coronary event rates) in US and non-US populations free of cardiovascular disease. METHODS: We reviewed studies that evaluated the performance of the Framingham risk score to predict first coronary events in a validation cohort, as identified by Medline, EMBASE, BIOSIS, and Cochrane library searches (through August 2005). Two reviewers independently assessed 1496 studies for eligibility, extracted data, and performed quality assessment using predefined forms. RESULTS: We included 25 validation cohorts of different population groups (n = 128,000) in our main analysis. Calibration varied over a wide range from under- to overprediction of absolute risk by factors of 0.57 to 2.7. Risk prediction for 7 cohorts (n = 18658) from the United States, Australia, and New Zealand was well calibrated (corresponding figures: 0.87-1.08; for the 5 biggest cohorts). The estimated population risks for first coronary events were strongly associated (goodness of fit: R2 = 0.84) and in good agreement with observed risks (coefficient for predicted risk: beta = 0.84; 95% CI 0.41-1.26). In 18 European cohorts (n = 109499), the corresponding figures indicated close association (R2 = 0.72) but substantial overprediction (beta = 0.58, 95% CI 0.39-0.77). The risk score was well calibrated on the intercept for both population clusters. CONCLUSION: The Framingham score is well calibrated to predict first coronary events in populations from the United States, Australia, and New Zealand. Overestimation of absolute risk in European cohorts requires recalibration procedures.

[The study of apoptosis factors released from laser injured cartilage inducing apoptosis of chondrocyte]

OBJECTIVE: To explore the role of pro-apoptotic signals following tissue injury and how these may promote a progression of further cell death. METHODS: Laser treated porcine articular cartilage disks were maintained in culture media. The collected media at various time periods (3, 6, 9, 12, 24 and 48 h), was called treated conditioned media (TCM). Non-laser treated cartilage disks were used to create control conditioned media (CCM). Each disk was subsequently maintained for 28 days and used in confocal microscopic assessment to document the progression of the damaged area. Isolated porcine chondrocytes were cultured in monolayer, and were exposed to TCM, CCM or normal culture medium (NM). As a positive inducer of apoptosis, the monolayer cells were exposed to UV radiation for 10 min and cultured in NM. Following 24 h exposure, the cells were harvested and stained with the appropriate combination of fluorescent dyes and processed via flow cytometry. RESULTS: All cultured cells exposed to TCM displayed a caspase-3 positive subpopulation, a loss of CMXRos, and with a reduced or lost NO signal. CCM exposure signals were comparable to the NM treatments with all having retained CMXRos, NO and without evidence of caspase-3 activity. UV treatment also induced a reduction in NO, but both CMXRos and caspase-3 positive, representing an earlier stage of apoptosis and suggesting that the mode of cell death via UV and TCM exposure are via different processes. The investigation of a dose (100%, 50%, 25% and 12.5%) and time (0.5, 1, 3, 9, 12 h) response to TCM exhibited that all treatments observed an increase in caspase-3 positive cells and a reduction in NO and CMXRos. CONCLUSION: The usefulness of FCM can be used in the study of cell viability and apoptosis. Such a system may be useful in the study of mechanisms of disease such as osteoarthritis, thus may be of practical use for the pharmaceutical industry for screening associated drugs.

[Does cataract surgery increase the risk of exudative age-related macular degeneration? Results from a large retrospective case-control study]

BACKGROUND: Many epidemiological studies indicate a positive correlation between cataract surgery and the subsequent progression of age-related macular degeneration (AMD). Such a correlation would have far-reaching consequences. However, in epidemiological studies it is difficult to determine the significance of a single risk factor, such as cataract surgery. PATIENTS AND METHODS: We performed a retrospective case-control study of patients with new onset exudative age-related macular degeneration to determine if cataract surgery was a predisposing factor. A total of 1496 eyes were included in the study: 984 cases with new onset of exudative AMD and 512 control eyes with early signs of age-related maculopathy. Lens status (phakic or pseudophakic) was determined for each eye. RESULTS: There was no significant difference in lens status between study and control group (227/984 [23.1 %] vs. 112/512 [21.8 %] pseudophakic, p = 0.6487; OR = 1.071; 95 % CI = 0.8284-1.384). In cases with bilateral pseudophakia (n = 64) no statistically significant difference of the interval between cataract surgery in either eye and the onset of exudative AMD in the study eye was found (225.9 +/- 170.4 vs. 209.9 +/- 158.2 weeks, p = 0.27). CONCLUSIONS: Our results provide evidence that cataract surgery is not a major risk factor for the development of exudative AMD.

Intercomparison of C-14 Analysis of Carbonaceous Aerosols: Exercise 2009

Radiocarbon analysis of the carbonaceous aerosol allows an apportionment of fossil and non-fossil sources of airborne particulate matter (PM). A chemical separation of total carbon (TC) into its subfractions organic carbon (OC) and elemental carbon (EC) refines this powerful technique, as OC and EC originate from different sources and undergo different processes in the atmosphere. Although C-14 analysis of TC, EC, and OC has recently gained increasing attention, interlaboratory quality assurance measures have largely been missing, especially for the isolation of EC and OC. In this work, we present results from an intercomparison of 9 laboratories for C-14 analysis of carbonaceous aerosol samples on quartz fiber filters. Two ambient PM samples and 1 reference material (RM 8785) were provided with representative filter blanks. All laboratories performed C-14 determinations of TC and a subset of isolated EC and OC for isotopic measurement. In general, C-14 measurements of TC and OC agreed acceptably well between the laboratories, i.e. for TC within 0.015-0.025 (FC)-C-14 for the ambient filters and within 0.041 (FC)-C-14 for RM 8785. Due to inhomogeneous filter loading, RM 8785 demonstrated only limited applicability as a reference material for C-14 analysis of carbonaceous aerosols. C-14 analysis of EC revealed a large deviation between the laboratories of 28-79 as a consequence of different separation techniques. This result indicates a need for further discussion on optimal methods of EC isolation for C-14 analysis and a second stage of this intercomparison.