Ten-year results following treatment of intrabony defects with an enamel matrix protein derivative combined with either a natural bone mineral or a β-tricalcium phosphate

BACKGROUND The purpose of the present study is to evaluate the 10-year results following treatment of intrabony defects treated with an enamel matrix protein derivative (EMD) combined with either a natural bone mineral (NBM) or β-tricalcium phosphate (β-TCP). METHODS Twenty-two patients with advanced chronic periodontitis and displaying one deep intrabony defect were randomly treated with a combination of either EMD + NBM or EMD + β-TCP. Clinical evaluations were performed at baseline and at 1 and 10 years. The following parameters were evaluated: plaque index, bleeding on probing, probing depth, gingival recession, and clinical attachment level (CAL). The primary outcome variable was CAL. RESULTS The defects treated with EMD + NBM demonstrated a mean CAL change from 8.9 ± 1.5 mm to 5.3 ± 0.9 mm (P <0.001) and to 5.8 ± 1.1 mm (P <0.001) at 1 and 10 years, respectively. The sites treated with EMD + β-TCP showed a mean CAL change from 9.1 ± 1.6 mm to 5.4 ± 1.1 mm (P <0.001) at 1 year and 6.1 ± 1.4 mm (P <0.001) at 10 years. At 10 years two defects in the EMD + NBM group had lost 2 mm, whereas two other defects had lost 1 mm of the CAL gained at 1 year. In the EMD + β-TCP group three defects had lost 2 mm, whereas two other defects had lost 1 mm of the CAL gained at 1 year. Compared with baseline, at 10 years, a CAL gain of ≥3 mm was measured in 64% (i.e., seven of 11) of the defects in the EMD + NBM group and in 82% (i.e., nine of 11) of the defects in the EMD + β-TCP group. No statistically significant differences were found between the 1- and 10-year values in either of the two groups. Between the treatment groups, no statistically significant differences in any of the investigated parameters were observed at 1 and 10 years. CONCLUSION Within their limitations, the present findings indicate that the clinical improvements obtained with regenerative surgery using EMD + NBM or EMD + β-TCP can be maintained over a period of 10 years.

Histological evaluation of human intrabony periodontal defects treated with an unsintered nanocrystalline hydroxyapatite paste

OBJECTIVES The aim of the study was to clinically and histologically evaluate the healing of human intrabony defects treated with open flap surgery (OFD) and application of a new, resorbable, fully synthetic, unsintered, nanocrystalline, phase-pure hydroxyapatite (nano-HA). MATERIALS AND METHODS Six patients, each of them displaying very advanced intrabony defects around teeth scheduled for extraction due to advanced chronic periodontitis and further prosthodontic considerations, were included in the study. Following local anaesthesia, mucoperiosteal flaps were reflected; the granulation tissue was removed, and the roots were meticulously debrided by hand and ultrasonic instruments. A notch was placed at the most apical extent of the calculus present on the root surface or at the most apical part of the defect (if no calculus was present) in order to serve as a reference for the histological evaluation. Following defect fill with nano-HA, the flaps were sutured by means of mattress sutures to allow primary intention healing. At 7 months after regenerative surgery, the teeth were extracted together with some of their surrounding soft and hard tissues and processed for histological analysis. RESULTS The postoperative healing was uneventful in all cases. At 7 months following surgery, mean PPD reduction and mean CAL gain measured 4.0 ± 0.8 and 2.5 ± 0.8 mm, respectively. The histological analysis revealed a healing predominantly characterized by epithelial downgrowth. Limited formation of new cementum with inserting connective tissue fibers and bone regeneration occurred in three out of the six biopsies (i.e. 0-0.86 and 0-1.33 mm, respectively). Complete resorption of the nano-HA was found in four out of the six biopsies. A few remnants of the graft particles (either surrounded by newly formed mineralized tissue or encapsulated in connective tissue) were found in two out of the six biopsies. CONCLUSION Within their limits, the present results indicate that nano-HA has limited potential to promote periodontal regeneration in human intrabony defects. CLINICAL RELEVANCE The clinical outcomes obtained following surgery with OFD + nano-HA may not reflect true periodontal regeneration.

Dimensions of the Ascending Aorta in Conotruncal Heart Defects

Dilatation of the ascending aorta is an important sequel in conotruncal anomalies, such as tetralogy of Fallot (TOF) or d-transposition of the great arteries (TGA). We measured dimensions and their progression at different levels of the ascending aorta in 80 patients. In TOF patients, mean z-score for aortic annulus was 1.65 (range -3.16-6.47), for sinus 1.93 (range -2.28-5.39), for st-junction 4.15 (range 0.0-8.18), and for ascending aorta 3.51 (range -1.23-6.36). Over time, annulus z-scores increased in the univariate analysis [0.07/year, 95 % confidence interval (CI) 0.01-0.14; p = 0.02], and this was unique to male patients (0.08/year, 95 % CI 0.00-0.15; p = 0.05). z-scores of the ascending aorta decreased (-0.1/year, 95 % CI -0.18 to -0.02; p = 0.02), and this was confined to patients without aortic regurgitation (AR; -0.09/year, 95 % CI -0.18 to -0.01; p = 0.04). In TGA, mean z-score for the aortic annulus was 2.13 (range -3.71-8.39), for sinus 1.77 (range -3.04-6.69), for st-junction 1.01 (range -5.44-6.71), and for ascending aorta 0.82 (range -4.91-6.46). In bivariate analysis, annulus z-scores decreased in females (-0.14/year, 95 % CI -0.25 to -0.03; p = 0.01) and in patients without AR (-0.07/year, 95 % CI -0.14-0.0; p = 0.03). z-scores of the ascending aorta increased significantly in males (0.08/year, 95 % CI 0.0 to 0.16; p = 0.05) and in patients with AR (0.12/year, 95 % CI 0.03-0.21; p = 0.01). In conclusion, TOF and TGA z-scores of the ascending aorta differ significantly from those of the normal population. Progression of z-scores over time is influenced by diagnosis, sex, and presence of AR.

The medial based bi- or trilobed flap for repair of distal alar defects

BACKGROUND Reconstruction of defects of the lateral nasal ala might be challenging. Reconstruction with a bi- or trilobed flap is common. The laterally based bi- or trilobed flap for defects of the distal ala or lateral tip of the nose produces mostly tissue protrusion in the nasal groove which is aesthetically unpleasant. Why not use more the medially based bi- or trilobed flap? OBJECTIVE To describe the utility of bilobed and trilobed flaps for alar defects insisting on the design of medially based flaps. METHODS To show the technique and practical application for this kind of reconstruction. RESULTS The bi- and trilobed flaps are useful for defect repair between the lateral nasal tip and the distal ala. We observed that in most cases the flap based medially respects anatomical subunits better than the laterally based flap for medium-sized defects of the distal ala of the nose. CONCLUSION I suggest that the bi- and trilobed flaps for repair of the lateral tip/distal ala should more often be medially based. This flap has a specific indication and precise advantage compared to other reconstructions, especially to the laterally based multilobed flaps in this specific indication.

Clinical response to chemotherapy in oesophageal adenocarcinoma patients is linked to defects in mitochondria

Chemotherapeutic drugs kill cancer cells, but it is unclear why this happens in responding patients but not in non-responders. Proteomic profiles of patients with oesophageal adenocarcinoma may be helpful in predicting response and selecting more effective treatment strategies. In this study, pretherapeutic oesophageal adenocarcinoma biopsies were analysed for proteomic changes associated with response to chemotherapy by MALDI imaging mass spectrometry. Resulting candidate proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and investigated for functional relevance in vitro. Clinical impact was validated in pretherapeutic biopsies from an independent patient cohort. Studies on the incidence of these defects in other solid tumours were included. We discovered that clinical response to cisplatin correlated with pre-existing defects in the mitochondrial respiratory chain complexes of cancer cells, caused by loss of specific cytochrome c oxidase (COX) subunits. Knockdown of a COX protein altered chemosensitivity in vitro, increasing the propensity of cancer cells to undergo cell death following cisplatin treatment. In an independent validation, patients with reduced COX protein expression prior to treatment exhibited favourable clinical outcomes to chemotherapy, whereas tumours with unchanged COX expression were chemoresistant. In conclusion, previously undiscovered pre-existing defects in mitochondrial respiratory complexes cause cancer cells to become chemosensitive: mitochondrial defects lower the cells' threshold for undergoing cell death in response to cisplatin. By contrast, cancer cells with intact mitochondrial respiratory complexes are chemoresistant and have a high threshold for cisplatin-induced cell death. This connection between mitochondrial respiration and chemosensitivity is relevant to anticancer therapeutics that target the mitochondrial electron transport chain.

The effect of desmopressin on platelet function: a selective enhancement of procoagulant COAT platelets in patients with primary platelet function defects.

1-deamino-8-d-arginine vasopressin (desmopressin [DDAVP]) is clinically efficacious in patients with mild platelet function disorders but it is not known which mechanisms mediate this effect. Our aim was to evaluate the impact of in vivo DDAVP administration in these patients. We assessed von Willebrand factor (VWF), factor VIII, platelet activation and aggregation, platelet-dependent thrombin generation, and platelet intracellular Na(+)/Ca(2+) fluxes, before and 2 and 4 hours after DDAVP (0.3 µg/kg). We found (1) no significant changes for P-selectin expression, PAC-1 binding, δ-granule content and secretion, and platelet-aggregation; (2) significant decreases of secretion of α-granules and GPIIb-IIIa activation induced by adenosine 5'-diphosphate, convulxin, and thrombin; (3) significant increases of procoagulant platelets induced by convulxin/thrombin and platelet-dependent thrombin generation; and (4) significant increases of intracellular Na(+)/Ca(2+) concentrations. We show that in vivo DDAVP selectively and markedly enhances the ability to form procoagulant platelets and increases platelet-dependent thrombin generation by enhancing Na(+)/Ca(2+) mobilization. This report indicates that the beneficial hemostatic effect of DDAVP is not limited to an increase in large VWF multimers. An enhancement of platelet procoagulant activity appears to be an additional and (at least in platelet disorders) -possibly clinically relevant mechanism of DDAVP's action.

Birth defects among surviving children under seven years of age in Tianjin, China

Birth defects are a leading cause of infant mortality in the developed countries. They are also of increasing concern in many developing countries, such as China. However, prevalence and causes of birth defects in China are inadequately understood.^ The purpose of the present study was to estimated prevalence of birth defects in surviving children under seven years of age in Tianjin, China and investigate determinants of birth defects in the study area.^ The present study took place in Tianjin, China in 1986, involving 22,081 surviving children under seven years of age. Children with birth defects were ascertained through physical examinations by physicians during household visits and ascertainment of birth defects was verified through multiple sources. Of 22,081 surviving children, 524 had birth defects (23.7 per 1,000). The study noted a striking discrepancy in the prevalence of birth defects between urban and rural area. The prevalence of birth defects was 16.3 per 1,000 in the urban and 33.2 per 1,000 in the rural area.^ Using cases of birth defects ascertained from surviving children, a case-control study was carried out. The study observed that first-trimester maternal flu was associated with increased risk of both major and minor birth defects in children after controlling for other maternal factors (adjusted odds ratio (OR) = 8.7, 95% confidence interval (CI) = 4.3-17.3; OR = 3.6, 95% CI = 1.7-7.5). This association could be biased by different reporting of exposure between mothers of children with birth defects and mothers of children without defects. This study indicated that maternal flu was also associated with congenital heart defects and polydactyly after controlling for other maternal factors (adjusted OR = 32.3, 95% CI = 13.3-78.3; adjusted OR = 5.5, 95% CI = 1.1-27.7). The associations remained when affected controls (children with similar birth defects other than congenital heart defects or polydactyly) were used (adjusted OR = 4.3, 95% CI = 1.2-15.3; OR = 1.4, 95% CI = 1.4-7.9). A weak association between first-trimester vaginal bleeding and selected groups of birth defects was found in this study, but the association may be confounded by other factors. Maternal smoking during pregnancy was modestly associated with cleft lip with or without cleft palate (OR = 1.4, 95% = 0.4-4.9), but the association may be due to chance. Some major limitations in this study warrant caution in interpretation of the findings, especially the causal relation. ^

Neural tube defects in Mexican-Americans living on the US-Mexico border: The effects of folic acid and dietary folate

Neural tube defects (NTDs) are malformations of the developing brain and spinal cord; the most common are anencephaly and spina bifida. Evidence from many populations suggests that 50% of NTDs can be prevented through daily consumption of folic acid. A recent study has reported that folic acid may not protect populations of Mexican descent. This finding has serious implications for women living along the US-Mexico border. Not only is risk high in these Mexican American women compared with other US women; they also differ markedly in supplemental folic acid and dietary folate consumption, and in NTD-related risks (e.g., obesity, diabetes). This case-control study investigated whether folic acid supplements and dietary folate reduces NTDs in Mexican Americans. Cases included liveborn, stillborn, electively and spontaneously aborted NTD-affected fetuses and infants occurring in the 14-county Texas-Mexico border. Controls were randomly selected from unaffected live births, frequency matched to cases by hospital and year. An in-person interview of 110 case and 113 control mothers solicited data on folic acid supplements, dietary folate, and other covariates. Consumption of folic acid-containing vitamins before conception was only 5% for both case and control women. Taking vitamins the trimester before conception had no apparent effect, after adjusting for covariates [odds ratio (OR) = 1.0, 95% confidence interval (CI) = 0.3–3.4]. Combining folate from vitamins and diet showed a 20% risk reduction for women consuming at least 400 μg of folate daily [OR = 0.8, 95% CI = 0.5–1.5]; however, this estimate is statistically indistinguishable from the null. Although consistent with an inherent ineffectiveness of supplemental folic acid, that so few women consumed multivitamins during the critical time severely limited the assessment of folic acid in this population. A reduced folate response in Mexican descent women may be due to a genetic heterogeneity for metabolizing folate. Alternatively, folate intakes may be insufficient to overcome other underlying risk factors. In conclusion, determining whether folic acid reduces NTD risk in Mexican American women requires further study in populations with higher folic acid exposures. Meanwhile, we should pursue all recommended prevention strategies to reduce risk, including motivating Mexican American women of childbearing age to take folic acid routinely. ^

Effect of pulverized natural bone mineral on regeneration of three-wall intrabony defects. A preclinical study.

AIMS The objective of this study is to evaluate the effects of a paste-like bone substitute material with easy handling properties and improved mechanical stability on periodontal regeneration of intrabony defects in dogs. MATERIALS AND METHODS Mandibular and maxillary first and third premolars were extracted, and three-wall intrabony defects were created on second and fourth premolars. After a healing period of 3 months, acute type defects were filled with a paste-like formulation of deproteinized bovine bone mineral (DBBM) (particle size, 0.125-0.25 mm) in a collagenous carrier matrix (T1), pulverized DBBM (particle size, 0.125-0.25 mm) without the carrier (T2), or Bio-Oss® granules (particle size, 0.25-1.00 mm) as control (C). All defects were covered with a Bio-Gide® membrane. The dogs were sacrificed after 12 weeks, and the specimens were analyzed histologically and histometrically. RESULTS Postoperative healing of all defects was uneventful, and no histological signs of inflammation were observed in the augmented and gingival regions. New cementum, new periodontal ligament, and new bone were observed in all three groups. The mean vertical bone gain was 3.26 mm (T1), 3.60 mm (T2), and 3.81 mm (C). That of new cementum was 2.25 mm (T1), 3.88 mm (T2), and 3.53 mm (C). The differences did not reach statistical significance. The DBBM particles were both incorporated in new bone and embedded in immature bone marrow. CONCLUSIONS The results of this preclinical study showed that the 0.125-0.25-mm DBBM particles in a powder or paste formulation resulted in periodontal regeneration comparable to the commercially available DBBM. Osteoconductivity, in particular, was not affected by DBBM size or paste formulation. CLINICAL RELEVANCE The improved handling properties of the paste-like bone substitute consisting of small DBBM particles embedded in a collagen-based carrier hold promise for clinical applications.

Effects of enamel matrix proteins in combination with a bovine-derived natural bone mineral for the repair of bone defects.

OBJECTIVES Previously, the use of enamel matrix derivative (EMD) in combination with a natural bone mineral (NBM) was able to stimulate periodontal ligament cell and osteoblast proliferation and differentiation. Despite widespread use of EMD for periodontal applications, the effects of EMD on bone regeneration are not well understood. The aim of the present study was to test the ability of EMD on bone regeneration in a rat femur defect model in combination with NBM. MATERIALS AND METHODS Twenty-seven rats were treated with either NBM or NBM + EMD and assigned to histological analysis at 2, 4, and 8 weeks. Defect morphology and mineralized bone were assessed by μCT. For descriptive histology, hematoxylin and eosin staining and Safranin O staining were performed. RESULTS Significantly more newly formed trabecular bone was observed at 4 weeks around the NBM particles precoated with EMD when compared with NBM particles alone. The drilled control group, in contrast, achieved minimal bone regeneration at all three time points (P < 0.05). CONCLUSIONS The present results may suggest that EMD has the ability to enhance the speed of new bone formation when combined with NBM particles in rat osseous defects. CLINICAL RELEVANCE These findings may provide additional clinical support for the combination of EMD with bone graft for the repair of osseous and periodontal intrabony defects.

Clinical outcomes following regenerative therapy of non-contained intrabony defects using a deproteinized bovine bone mineral combined with either enamel matrix derivative or collagen membrane

BACKGROUND The purpose of this study is to compare clinical outcomes in the treatment of deep non-contained intrabony defects (i.e., with ≥70% 1-wall component and a residual 2- to 3-wall component in the most apical part) using deproteinized bovine bone mineral (DBBM) combined with either enamel matrix protein derivative (EMD) or collagen membrane (CM). METHODS Forty patients with multiple intrabony defects were enrolled. Only one non-contained defect per patient with an intrabony depth ≥3 mm located in the interproximal area of single- and multirooted teeth was randomly assigned to the treatment with either EMD + DBBM (test: n = 20) or CM + DBBM (control: n = 20). At baseline and after 12 months, clinical parameters including probing depth (PD) and clinical attachment level (CAL) were recorded. The primary outcome variable was the change in CAL between baseline and 12 months. RESULTS At baseline, the intrabony component of the defects amounted to 6.1 ± 1.9 mm for EMD + DBBM and 6.0 ± 1.9 mm for CM + DBBM sites (P = 0.81). The mean CAL gain at sites treated with EMD + DBBM was not statistically significantly different (P = 0.82) compared with CM + DBBM (3.8 ± 1.5 versus 3.7 ± 1.2 mm). No statistically significant difference (P = 0.62) was observed comparing the frequency of CAL gain ≥4 mm between EMD + DBBM (60%) and CM + DBBM (50%) or comparing the frequency of residual PD ≥6 mm between EMD + DBBM (5%) and CM + DBBM (15%) (P = 0.21). CONCLUSION Within the limitations of the present study, regenerative therapy using either EMD + DBBM or CM + DBBM yielded comparable clinical outcomes in deep non-contained intrabony defects after 12 months.

Which biomaterials may promote periodontal regeneration in intrabony periodontal defects? A systematic review of preclinical studies.

OBJECTIVE To systematically analyze the regenerative effect of the available biomaterials either alone or in various combinations for the treatment of periodontal intrabony defects as evaluated in preclinical histologic studies. DATA SOURCES A protocol covered all aspects of the systematic review methodology. A literature search was performed in Medline, including hand searching. Combinations of searching terms and several criteria were applied for study identification, selection, and inclusion. The preliminary outcome variable was periodontal regeneration after reconstructive surgery obtained with the various regenerative materials, as demonstrated through histologic/ histomorphometric analysis. New periodontal ligament, new cementum, and new bone formation as a linear measurement in mm or as a percentage of the instrumented root length were recorded. Data were extracted based on the general characteristics, study characteristics, methodologic characteristics, and conclusions. Study selection was limited to preclinical studies involving histologic analysis, evaluating the use of potential regenerative materials (ie, barrier membranes, grafting materials, or growth factors/proteins) for the treatment of periodontal intrabony defects. Any type of biomaterial alone or in various combinations was considered. All studies reporting histologic outcome measures with a healing period of at least 6 weeks were included. A meta-analysis was not possible due to the heterogeneity of the data. CONCLUSION Flap surgery in conjunction with most of the evaluated biomaterials used either alone or in various combinations has been shown to promote periodontal regeneration to a greater extent than control therapy (flap surgery without biomaterials). Among the used biomaterials, autografts revealed the most favorable outcomes, whereas the use of most biologic factors showed inferior results compared to flap surgery.