Healing of two and three wall intrabony periodontal defects following treatment with an enamel matrix derivative combined with autogenous bone

BACKGROUND: There are still limited data on the outcomes of regenerative periodontal surgery using a combination of an enamel matrix protein derivative (EMD) and autogenous bone (AB). AIM: To evaluate the healing of deep intrabony defects treated with either a combination EMD+AB or EMD alone. MATERIALS AND METHODS: Forty patients with advanced chronic periodontitis, with one deep intrabony defect, were randomly treated with either EMD+AB (test) or EMD (control). Clinical assessments were performed at baseline and at 1 year after treatment. The primary outcome variable was relative attachment level (RAL). RESULTS: Healing was uneventful in all patients. The test sites showed a reduction in the mean probing pocket depth (PPD) of 5.6 +/- 0.9 mm (p<0.001), a gain in the mean RAL of 4.2 +/- 1.1 mm (p<0.001) and a gain in the mean probing bone level (PBL) of 3.9 +/- 1.0 mm (p<0.001). The control group displayed a mean PPD reduction of 4.6 +/- 0.4 mm (p<0.001), a mean RAL gain of 3.4 +/- 0.8 mm (p<0.001) and a mean PBL gain of 2.8 +/- 0.8 mm (p<0.001). RAL gains of > or =4 mm were measured in 90% of the test defects and in 55% of the controls. PBL gains of > or =4 mm were obtained in 85% of the test defects and in 25% of the control ones. The test treatment resulted in statistically higher PPD reductions, RAL gains and PBL gains compared with the control (p<0.01). CONCLUSIONS: Within their limits, the present results indicate that: (i) at 1 year after surgery, both therapies resulted in statistically significant clinical improvements compared with baseline and (ii) although the combination of EMD+AB resulted in statistically significant higher soft and hard tissue improvements compared with treatment with EMD, the clinical relevance of this finding is unclear.

23Na MR imaging at 7 T after knee matrix-associated autologous chondrocyte transplantation: preliminary results

To evaluate the feasibility of sodium 7-T magnetic resonance (MR) imaging in repaired tissue and native cartilage of patients after matrix-associated autologous chondrocyte transplantation (MACT) and compare results with delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC) at 3 T.

Bovine pericardium based non-cross linked collagen matrix for successful root coverage, a clinical study in human

Introduction The aim of this study was to clinically assess the capacity of a novel bovine pericardium based, non-cross linked collagen matrix in root coverage. Methods 62 gingival recessions of Miller class I or II were treated. The matrix was adapted underneath a coronal repositioned split thickness flap. Clinical values were assessed at baseline and after six months. Results The mean recession in each patient was 2.2 mm at baseline. 6 Months after surgery 86.7% of the exposed root surfaces were covered. On average 0,3 mm of recession remained. The clinical attachment level changed from 3.5 ± 1.3 mm to 1,8 ( ± 0,7) mm during the observational time period. No statistically significant difference was found in the difference of probing depth. An increase in the width of gingiva was significant. With a baseline value of 1.5 ± 0.9 mm an improvement of 2.4 ± 0.8 mm after six month could be observed. 40 out of 62 recessions were considered a thin biotype at baseline. After 6 months all 62 sites were assessed thick. Conclusions The results demonstrate the capacity of the bovine pericardium based non-cross linked collagen matrix for successful root coverage. This material was able to enhance gingival thickness and the width of keratinized gingiva. The percentage of root coverage achieved thereby is comparable to existing techniques. This method might contribute to an increase of patient's comfort and an enhanced aesthetical outcome.

Four-year results following treatment of intrabony periodontal defects with an enamel matrix derivative alone or combined with a biphasic calcium phosphate

The aim of this study was to evaluate the 4-year clinical outcomes following regenerative surgery in intrabony defects with either EMD + BCP or EMD. Twenty-four patients with advanced chronic periodontitis, displaying one-, two-, or three-walled intrabony defect with a probing depth of at least 6 mm, were randomly treated with either EMD + BCP (test) or EMD alone (control). The following clinical parameters were evaluated at baseline, at 1 year and at 4 years after regenerative surgery: plaque index, gingival index, bleeding on probing, probing depth, gingival recession, and clinical attachment level (CAL). The primary outcome variable was CAL. No differences in any of the investigated parameters were observed at baseline between the two groups. The test group demonstrated a mean CAL change from from 10.8 ± 1.6 mm to 7.4 ± 1.6 mm (p < 0.001) and to 7.6 ± 1.7 mm (p < 0.001) at 1 and 4 years, respectively. In the control group, mean CAL changed from 10.4 ± 1.3 at baseline to 6.9 ± 1.0 mm (p < 0.001) at 1 year and 7.2 ± 1.2 mm (p < 0.001) at 4 years. At 4 years, two defects in the test group and three defects in the control group have lost 1 mm of the CAL gained at 1 year. Compared to baseline, at 4 years, a CAL gain of ≥3 mm was measured in 67% of the defects (i.e., in 8 out of 12) in the test group and in 75% of the defects (i.e., in 9 out of 12) in the control group. There were no statistically significant differences in any of the investigated parameters at 1 and at 4 years between the two groups. Within their limits, the present results indicate that: (a) the clinical improvements obtained with both treatments can be maintained over a period of 4 years, and (b) in two- and three-walled intrabony defects, the addition of BCP did not additionally improve the outcomes obtained with EMD alone. In two- and three-walled intrabony defects, the combination of EMD + BCP did not show any advantage over the use of EMD alone.

Putative functions of extracellular matrix glycoproteins in secondary palate morphogenesis

Cleft palate is a common birth defect in humans. Elevation and fusion of paired palatal shelves are coordinated by growth and transcription factors, and mutations in these can cause malformations. Among the effector genes for growth factor signaling are extracellular matrix (ECM) glycoproteins. These provide substrates for cell adhesion (e.g., fibronectin, tenascins), but also regulate growth factor availability (e.g., fibrillins). Cleft palate in Bmp7 null mouse embryos is caused by a delay in palatal shelf elevation. In contrast, palatal shelves of Tgf-β3 knockout mice elevate normally, but a cleft develops due to their failure to fuse. However, nothing is known about a possible functional interaction between specific ECM proteins and Tgf-β/Bmp family members in palatogenesis. To start addressing this question, we studied the mRNA and protein distribution of relevant ECM components during secondary palate development, and compared it to growth factor expression in wildtypewild type and mutant mice. We found that fibrillin-2 (but not fibrillin-1) mRNA appeared in the mesenchyme of elevated palatal shelves adjacent to the midline epithelial cells, which were positive for Tgf-β3 mRNA. Moreover, midline epithelial cells started expressing fibronectin upon contact of the two palatal shelves. These findings support the hypothesis that fibrillin-2 and fibronectin are involved in regulating the activity of Tgf-β3 at the fusing midline. In addition, we observed that tenascin-W (but not tenascin-C) was misexpressed in palatal shelves of Bmp7-deficient mouse embryos. In contrast to tenascin-C, tenascin-W secretion was strongly induced by Bmp7 in embryonic cranial fibroblasts in vitro. These results are consistent with a putative function for tenascin-W as a target of Bmp7 signaling during palate elevation. Our results indicate that distinct ECM proteins are important for morphogenesis of the secondary palate, both as downstream effectors and as regulators of Tgf-β/Bmp activity.

Gelatinase B [matrix metalloproteinase (MMP)-9] and collagenases (MMP-8/-13) are upregulated in cerebrospinal fluid during aseptic and bacterial meningitis in children

We investigated the protein expression of gelatinases [matrix metalloproteinase (MMP)-2 and -9] and collagenases (MMP-8 and -13) in cerebrospinal fluid (CSF) from patients with bacterial (BM, n = 17) and aseptic (AM, n = 14) meningitis. In both, MMP-8 and -9 were increased in 100% of patients, whereas MMP-13 was detectable in 53% and 82% respectively. Three patients with clinical signs of meningitis, without CSF pleocytosis, scored positive for all three MMPs. MMP-8 appeared in two isoforms, granulocyte-type [polymorphonuclear cell (PMN)] and fibroblast/macrophage (F/M) MMP-8. Analysis of kinetic changes from serial lumbar punctures showed that these MMPs are independently regulated, and correlate only partly with CSF cytosis or levels of the endogenous inhibitor, tissue inhibitor of matrix metalloproteinase-1. In vitro, T cells, peripheral blood mononuclear cells (PBMCs) and granulocytes (PMN) release MMP-8 and -9, whereas MMP-13 could be found only in the former two cell types. Using models of exogenous (n-formyl-Met-Leu-Phe, T cell receptor cross-linking) and host-derived stimuli (interleukin-2), the kinetics and the release of the MMP-8, -9 and -13 showed strong variation between these immune cells and suggest release from preformed stocks. In addition, MMP-9 is also synthesized de novo in PBMCs and T cells. In conclusion, invading immune cells contribute only partially to MMPs in CSF during meningitis, and parenchymal cells are an equally relevant source. In this context, in patients with clinical signs of meningitis, but without CSF pleocytosis, MMPs seem to be a highly sensitive marker for intrathecal inflammation. The present data support the concept that broad-spectrum enzyme inhibition targeting gelatinases and collagenases is a potential strategy for adjunctive therapy in infectious meningitis.

Should 3K zoom function be used for detection of pneumothorax in cesium iodide/amorphous silicon flat-panel detector radiographs presented on 1K-matrix soft copies?

The purpose of the study was to evaluate observer performance in the detection of pneumothorax with cesium iodide and amorphous silicon flat-panel detector radiography (CsI/a-Si FDR) presented as 1K and 3K soft-copy images. Forty patients with and 40 patients without pneumothorax diagnosed on previous and subsequent digital storage phosphor radiography (SPR, gold standard) had follow-up chest radiographs with CsI/a-Si FDR. Four observers confirmed or excluded the diagnosis of pneumothorax according to a five-point scale first on the 1K soft-copy image and then with help of 3K zoom function (1K monitor). Receiver operating characteristic (ROC) analysis was performed for each modality (1K and 3K). The area under the curve (AUC) values for each observer were 0.7815, 0.7779, 0.7946 and 0.7066 with 1K-matrix soft copies and 0.8123, 0.7997, 0.8078 and 0.7522 with 3K zoom. Overall detection of pneumothorax was better with 3K zoom. Differences between the two display methods were not statistically significant in 3 of 4 observers (p-values between 0.13 and 0.44; observer 4: p = 0.02). The detection of pneumothorax with 3K zoom is better than with 1K soft copy but not at a statistically significant level. Differences between both display methods may be subtle. Still, our results indicate that 3K zoom should be employed in clinical practice.

Inhibition of matrix metalloproteinases and tumour necrosis factor alpha converting enzyme as adjuvant therapy in pneumococcal meningitis

Matrix metalloproteinases (MMPs) and tumour necrosis factor alpha (TNF-alpha) converting enzyme (TACE) contribute synergistically to the pathophysiology of bacterial meningitis. TACE proteolytically releases several cell-surface proteins, including the proinflammatory cytokine TNF-alpha and its receptors. TNF-alpha in turn stimulates cells to produce active MMPs, which facilitate leucocyte extravasation and brain oedema by degradation of extracellular matrix components. In the present time-course studies of pneumococcal meningitis in infant rats, MMP-8 and -9 were 100- to 1000-fold transcriptionally upregulated, both in CSF cells and in brain tissue. Concentrations of TNF-alpha and MMP-9 in CSF peaked 12 h after infection and were closely correlated. Treatment with BB-1101 (15 mg/kg subcutaneously, twice daily), a hydroxamic acid-based inhibitor of MMP and TACE, downregulated the CSF concentration of TNF-alpha and decreased the incidences of seizures and mortality. Therapy with BB-1101, together with antibiotics, attenuated neuronal necrosis in the cortex and apoptosis in the hippocampus when given as a pretreatment at the time of infection and also when administration was started 18 h after infection. Functionally, the neuroprotective effect of BB-1101 preserved learning performance of rats assessed 3 weeks after the disease had been cured. Thus, combined inhibition of MMP and TACE offers a novel therapeutic strategy to prevent brain injury and neurological sequelae in bacterial meningitis.

Matrix metalloproteinases contribute to brain damage in experimental pneumococcal meningitis

The present study was performed to evaluate the role of matrix metalloproteinases (MMP) in the pathogenesis of the inflammatory reaction and the development of neuronal injury in a rat model of bacterial meningitis. mRNA encoding specific MMPs (MMP-3, MMP-7, MMP-8, and MMP-9) and the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) were significantly (P < 0.04) upregulated, compared to the beta-actin housekeeping gene, in cortical homogenates at 20 h after infection. In parallel, concentrations of MMP-9 and TNF-alpha in cerebrospinal fluid (CSF) were significantly increased in rats with bacterial meningitis compared to uninfected animals (P = 0.002) and showed a close correlation (r = 0.76; P < 0. 001). Treatment with a hydroxamic acid-type MMP inhibitor (GM6001; 65 mg/kg intraperitoneally every 12 h) beginning at the time of infection significantly lowered the MMP-9 (P < 0.02) and TNF-alpha (P < 0.02) levels in CSF. Histopathology at 25.5 +/- 5.7 h after infection showed neuronal injury (median [range], 3.5% [0 to 17.5%] of the cortex), which was significantly (P < 0.01) reduced to 0% (0 to 10.8%) by GM6001. This is the first report to demonstrate that MMPs contribute to the development of neuronal injury in bacterial meningitis and that inhibition of MMPs may be an effective approach to prevent brain damage as a consequence of the disease.

Steady-state diffusion imaging for MR in-vivo evaluation of reparative cartilage after matrix-associated autologous chondrocyte transplantation at 3 tesla--preliminary results

OBJECTIVES: To demonstrate the feasibility of time-reversed fast imaging with steady-state precession (FISP) called PSIF for diffusion-weighted imaging of cartilage and cartilage transplants in a clinical study. MATERIAL AND METHODS: In a cross-sectional study 15 patients underwent MRI using a 3D partially balanced steady-state gradient echo pulse sequence with and without diffusion weighting at two different time points after matrix-associated autologous cartilage transplantation (MACT). Mean diffusion quotients (signal intensity without diffusion-weighting divided by signal intensity with diffusion weighting) within the cartilage transplants were compared to diffusion quotients found in normal cartilage. RESULTS: The global diffusion quotient found in repair cartilage was significantly higher than diffusion values in normal cartilage (p<0.05). There was a decrease between the earlier and the later time point after surgery. CONCLUSIONS: In-vivo diffusion-weighted imaging based on the PSIF technique is possible. Our preliminary results show follow-up of cartilage transplant maturation in patients may provide additional information to morphological assessment.