Long-term follow-up of camouflage effects following resin infiltration of post orthodontic white-spot lesions in vivo

Objectives:To reassess the long-term camouflage effects of resin infiltration (Icon, DMG, Hamburg, Germany) of white spot lesions (WSL) and sound adjacent enamel (SAE) achieved in a previous trial. The null hypothesis was tested that there were no significantly different CIE-L*a*b*-ΔE-values between WSL and SAE areas of assessment after at least 24 months (T24) compared to those at baseline (T0).Materials and Methods:Of twenty subjects who received previous resin infiltration treatment of n_teeth = 111 nonrestored, noncavitated postorthodontic WSL after multibracket treatment during a randomized controlled trial and were contacted 20 months after baseline, eight subjects (trial teeth n_teeth = 40; m/f ratio 1/7; age range (mean; SD) 12–17 [15.25; 2.12] years); response rate: 40%) were available for follow-up after at least 24 months (T24). CIE-L*a*b* differences between summarized color and lightness values (ΔE_WSL/SAE) of WSL and SAE were assessed using a spectrophotometer and compared to baseline data assessed prior to infiltration (T0), and those after 6 (T6), and 12 (T12) months using paired t tests at a significance level of α = 5%.Results:T24 assessments were performed after a mean 33.86 (SD: 8.64; Min: 24; Max: 45) months following T0. Mean (SD) ΔE_WSL/SAE units of available teeth were 8.76 (5.33) at baseline; 5.5 (2.75) at T6; 5.2 (2.41) at T12; and 5.57 (2.6) at T24. Comparisons of T6, T12, and T24 with T0 yielded highly significant differences, whereas T6–T24 and T12–T24 differences were found to be not significant.Conclusions:Assimilation of infiltrated WSL to the color of adjacent enamel by resin infiltration is considered to be suitable for the long-term improvement in the esthetic appearance of postorthodontic WSL.     

Normative values of bone parameters of children and adolescents using digital computer-assisted radiogrammetry (DXR).

PURPOSE: To verify whether estimation of bone mineral density (BMD) using digital X-ray radiogrammetry (DXR) is possible on children and to determine normative values of both such a DXR-BMD estimate and a corresponding metacarpal index (DXR-MCI) on. PATIENTS AND METHODS: In retrospect, X-rays were selected of the hands of 200 healthy Caucasian children (120 boys and 80 girls, aged 4-18 yr). The involved children were selected among a larger group of children submitted to the surgical department of our institute for evaluation of a suspected fracture after an occurred trauma. All children with a verified fracture or a chronic bone-related disease, including bone age retardation or acceleration, were excluded from the study. Furthermore, only conventional X-rays with the same film and capture parameters were included. The images were scanned and analyzed using the Pronosco X-posure system V.2 (Sectra Pronosco, Denmark). DXR-BMD, DXR-MCI, and a porosity index (DXR-PI) were automatically calculated using the midshafts of the metacarpals II-IV. Mean values of DXR-BMD and DXR-MCI were calculated separately for girls and boys in 2-yr intervals. RESULTS: In the present study the system has been demonstrated to be capable of calculating DXR-BMD from conventional X-rays of the hand from children down to approx 6 yr of age. This ability depended somewhat on the diameter and the length of the involved metacarpals. The success rate was higher for large bones than for small bones. The system succeeded in analyzing the images of 110 boys and 68 girls. Values of DXR-BMD were observed to increase with age from 0.40 g/cm2 to 0.62 g/cm2 in the male group and from 0.39 g/cm2 to 0.54 g/cm2 in the female group. Girls aged 11-12 yr had a higher DXR-BMD than did boys, corresponding to the earlier entry to puberty of girls. Standard deviations (SDs) reached values of up to 0.05 g/cm2. DXR-MCI increased with age from 0.36 to 0.47 for boys and from 0.34 to 0.49 for girls with a maximum SD of 0.06. The correlation between DXR-BMD and age was r=0.83 and r=0.84 for boys and girls, respectively. The corresponding correlations for DXR-MCI was lower, with observed correlations of r=0.63 (boys) and r=0.68 (girls), respectively, with p<0.01 in all cases. The DXR-PI did not reveal a significant correlation to age (r=-0.31 and r=0.04. respectively) and showed SDs marginally higher than the calculated mean values. CONCLUSION: The newly available DXR-methodology seems to offer the ability to determine DXR-BMD and DXR-MCI in children starting with a bone age of 6. This possibility may be of special relevance for children suffering from chronic bone diseases that require repeated X-rays of the hand (e.g. to determine bone age). The acquired normative data suggest that the measurements are of clinical value owing to low age-dependent variability (SDs) relative to an observed high increase with age. The clinical value of the porosity index (DXR-PI) remains uncertain and is limited owing to a high inter-individual variability.     

New aspects of the etiology of tendon rupture

Summary Native collagen fibers were exposed to different dynamic loads to simulate damage to tendons and ligaments relevant clinically and for sports medicine. The results suggest that the rupture of a tendon is caused at the submicroscopic fibrillar level. Not only slow or very fast elongation, but also very fast unloading of stretched fibers seems to be responsible for disseminated damage, which reduces the stability of a fiber. This damage is induced by intrafibrillar sliding processes, which occur only a few seconds before macroscopic slippage takes place. The significance of these events for the beginning and progress of repair in vivo is discussed. The conclusions are supported by simultaneous mechanical and radiological measurements, as well as by light- and electron-microscopic results.

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Zusammenfassung Zur Simulierung klinisch bzw. sportmedizinisch relevanter Schäden an Sehnen und Bändern wurden native Kollagenfasern unterschiedlichen dynamischen Belastungen ausgesetzt. Die erzielten Ergebnisse sprechen dafür, die Ursachen einer Sehnenruptur im submikroskopischen fibrillären Bereich zu suchen. Sowohl eine langsame oder ruckartige Dehnung als auch eine ruckartige Entlastung zugbelasteter Fasern scheinen für das Auftreten disseminierter, die Faserstabilität reduzierender Gefügestörungen verantwortlich zu sein. Diese Gefügestörungen werden durch intrafibrilläre Gleitvorgänge eingeleitet, die an den noch voll belastbaren Fasern nur wenige Sekunden vor dem Einsetzen eines makroskopischen Faserfließens auftreten. Die Bedeutung dieser Ereignisse für den Beginn und Verlauf einer in vivo stattfindenden Reparationsphase wird erörtert. Die Aussagen werden gestützt durch simultane mechanische und röntgenographische Messungen sowie durch makroskopische, licht- und elektronenmikroskopische Befunde.

     

Differences in CMV-Specific T-Cell Levels and Long-Term Susceptibility to CMV Infection after Kidney, Heart and Lung Transplantation

Patients after kidney, heart and lung transplantation differ in their immunosuppressive drug regimens and in susceptibility to infectious complications with cytomegalovirus (CMV). In this study, CMV-specific T-cell responses were characterized in long-term transplant recipients and associated with the frequency of infectious complications. CMV-reactive CD4 T cells from 50 healthy controls, 68 renal, 14 heart and 24 lung transplant recipients were flow cytometrically quantified by the induction of cytokines after specific stimulation. Moreover, the immunosuppressive effect of calcineurin inhibitors on specific T-cell reactivity was quantified in vitro and compared with responses in vivo. Median CMV-specific T-cell frequencies in long-term renal (1.48%; range 0.06-17.26%) and heart transplant recipients (0.90%; 0.13-12.49%) did not differ from controls (1.82%; 0.26-21.00%). In contrast, CMV-specific T-cell levels were significantly lower in lung transplant recipients (0.50%; <0.05-4.98%) and showed a significant correlation with the frequency of infectious episodes (r =-0.57, p = 0.005). The differences within the groups were associated with increasing dosages of immunosuppressive drugs, as exemplified for calcineurin inhibitors that dose dependently reduced specific T-cell reactivity in vitro. In conclusion, monitoring CMV-specific CD4 T cells may serve as a measure for long-term disease susceptibility and may contribute to an improved management of CMV complications after lung transplantation.     

18F-FDG PET for mediastinal staging of lung cancer: which SUV threshold makes sense?

(18)F-FDG PET is the most accurate noninvasive modality for staging mediastinal lymph nodes in lung cancer. Besides using visual image interpretation, some institutions use standardized uptake value (SUV) measurements in lymph nodes. Mostly, an SUV of 2.5 is used as the cutoff, but this choice was never deduced from respective studies. Receiver operating characteristic (ROC) analyses demonstrated that SUV thresholds of more than 4 resulted in the highest accuracy. But these high cutoffs imply high false-negative rates (FNRs). The aim of our evaluation was to determine an optimal SUV threshold and to compare its diagnostic performance with the results of visual interpretation. METHODS: This retrospective study included 95 patients with suspected lung cancer who underwent mediastinoscopy/mediastinal lymphadenectomy after (18)F-FDG PET (90-150 min after 250 MBq of (18)F-FDG). Maximum SUV was measured in 371 lymph node regions biopsied afterward and visually interpreted using a 6-level score (- - - through + + +). Diagnostic performance was assessed by ROC analysis. FNR and false-positive rate (FPR), the sum of both error rates (FNR + FPR), and diagnostic accuracy were plotted against a hypothetical SUV threshold to determine the optimum SUV threshold. RESULTS: SUVs in metastatic lymph nodes were higher (mean +/- SD, 7.1 +/- 4.5; range, 1.4-26.9; n = 70) than in tumor-free lymph node stations (2.4 +/- 1.7; range, 0.6-14.9; n = 301; P < 0.01). Inflammatory lymph nodes exhibited slightly increased SUVs (2.7 +/- 2.0; range, 0.8-14.9; n = 146). The plot of error rates featured a minimum of the sum FNR + FPR for an SUV of 2.5. With increasing SUV threshold, the FPR decreased most prominently up to that value whereas a continuous rise of FNR was noticed. Highest diagnostic accuracy was achieved with an SUV of 4.5. The areas under the ROC curves demonstrated that visual interpretation tends to be more accurate than SUV quantification (visual, 0.930 +/- 0.022; SUV, 0.899 +/- 0.025; P = 0.241). Using an SUV of 2.5 as the threshold, the resulting sensitivity, specificity, and negative predictive value were 89%, 84%, and 96%, respectively. CONCLUSION: For mediastinal staging, the choice of an SUV of 2.5 as the threshold is justified because FNR + FPR is minimized. The resulting high negative predictive value of 96% allows the omission of mediastinoscopy in patients with negative mediastinal findings on (18)F-FDG PET images. For the experienced observer, visual analysis should be relied on primarily, with calculation of the SUV used, at most, as a secondary aid. For the less experienced observer, the SUV may be of greater value.     

Diagnostic relevance of Langerin detection in cells from bronchoalveolar lavage of patients with pulmonary Langerhans cell histiocytosis,sarcoidosis and idiopathic pulmonary fibrosis

The diagnosis of pulmonary Langerhans cell histiocytosis might be refined by demonstrating reliability of a new cell marker, i.e., Langerin (CD207), used on bronchoalveolar lavage fluid. For this purpose, we collected material from patients with this disease and also with sarcoidosis and idiopathic pulmonary fibrosis as controls. In addition to the immunocytochemical detection of Langerin, we examined the expression profiles of CD1a and the macrophage tandem-repeat mannose receptor (CD206). To test accessibility of Langerin, a C-type lectin, for mannosides, we employed reverse lectin histochemistry using mannose-containing neoglycoproteins. The analysis revealed a significantly increased percentage of CD1a- and Langerin-positive cells in pulmonary Langerhans cell histiocytosis in comparison with both other studied diseases. No expression of the 175-kDa mannose-binding lectin (CD206) in Langerhans cells was observed. Evidently, binding sites on the cells were not accessible for the mannose-containing neoglycoligand. These results provide evidence for the usefulness of Langerin-directed immuno- and glycohistochemical monitoring of bronchoalveolar lavage fluid in the diagnosis of pulmonary Langerhans cell histiocytosis.     

The developmentally regulated neural crest-associated glycotope HNK-1 predicts metastasis in cutaneous malignant melanoma

Aberrant glycosylation is a common feature of metastatic sub-clones of malignant tumours and in uveal melanoma in particular, the HNK-1 glycotope has been positively correlated with poor prognosis. So far, no such correlation has been investigated in cutaneous melanoma. In order to do so, HNK-1 expression was evaluated immunohistochemically in 100 primary cutaneous melanomas and correlated with metastasis after up to 10-years' follow-up. Furthermore, HNK-1 expression was analysed in metastatic deposits (19 distant cutaneous metastases and six sentinel lymph node metastases), as well as in benign nevi. Kaplan-Meier analysis revealed a positive association between HNK-1 expression and metastasis (p < 0.005) and multivariate Cox regression analysis adjusted for the standard prognostic markers ulceration and vertical tumour thickness confirmed HNK-1 expression as an independent prognostic marker. HNK-1 expression was preserved in 42% of the distant cutaneous metastases, but metastatic cells in lymph nodes were devoid of HNK-1 immunoreactivity. None of the benign pigmented lesions exhibited HNK-1 immunoreactivity. Expression of the HNK-1 glycotope in cutaneous malignant melanoma is an independent prognostic marker of metastasis. Differential HNK-1 expression at the metastatic sites implies that its expression is modulated by the surrounding environment. As HNK-1 is also transiently expressed during migration of melanocyte precursor cells derived from the neural crest, recapitulation of this transient expression might occur during metastatic spread of cutaneous malignant melanoma.     

Galectin-1 is overexpressed in nasal polyps under budesonide and inhibits eosinophil migration

Because of the importance of galectins for various cellular activities, the influence of the glucocorticoid budesonide on the level of expression of galectins-1 and -3 was investigated in human nasal polyposis. Ten nasal polyps obtained from surgical resection were maintained for 24 hours in the presence of various concentrations of budesonide. As quantitatively demonstrated by means of computer-assisted microscopy, 250 ng/ml (the highest dose tested) induced a pronounced increase of galectin-1 expression. This feature was observed in nasal polyps from allergic patients but not in those from nonallergic patients. Since eosinophils represent the main inflammatory cell population in nasal polyps, we investigated the effect of galectin-1 on their migration levels by means of quantitative phase-contrast computer-assisted videomicroscopy. Our results show that galectin-1 (coated on plastic supports) markedly reduced the migration levels of eosinophils in comparison to P-selectin. On the cellular level, marked modifications in the polymerization/depolymerization dynamics of the actin cytoskeleton (as revealed by means of computer-assisted fluorescence microscopy) and, to a much lesser extent, an increase in the adhesiveness of eosinophils to tested substrata were detectable. The present study therefore reveals a new galectin-1-mediated mechanism of action for glucocorticoid-mediated anti-inflammatory effects.