Closure of critical sized defects with allogenic and alloplastic bone substitutes

PURPOSE: This study evaluates bone regeneration of critical sized cranial vault defects in New Zealand white rabbits using four commercially available bone substitutes: OsteoSet (calcium sulphate pellets), DynaGraft Putty (demineralized bone matrix delivered in a poloxmer excipient), Norian CRS, and Bone Source (two commercially available calcium phosphate cements). MATERIALS AND METHODS: Critical sized defects 15 mm in diameter were created bilaterally in the parietal bones of 30 adult male New Zealand White rabbits. They were divided into three groups with ten animals in each. Bone healing was assessed clinically, radiographically, and histomorphometrically. Group 1 had calcium sulfate bioimplant on one side of the calvarium and an unfilled defect on the contralateral side. Group 2 had DBM putty on one side and Poloxamer gel on the contralateral side. Group 3, the Calcium phosphate cements (CPC), had Norian CRS on one side and Bone Source on the contralateral side. Five animals in each group were killed at 6 weeks and 12 weeks post operatively. RESULTS: All unfilled defects healed with fibrous scar, as did the Plaster of Paris and the poloxamer gel defects. Defects reconstructed with the demineralized bone matrix putty healed with bone throughout the entire defect. This was obvious clinically and radiographically where the defects appeared completely filled with a dense radiopaque tissue. The six-week group displayed new bone formation (87.1%) surrounding the remaining allogeneic particles. Resorption was evidenced by the presence of osteoclastic activity and by the significant decrease in the size of the demineralized bone particles. By 12 weeks, the demineralized bone putty bioimplant was almost completely replaced by new bone (95.5%). Both calcium phosphate cement groups (Norian CRS and Bone Source) had identical patterns of healing. They clinically were visible and firm and uniformly radiopaque with little evidence of new bone formation. Histologically the cement remained unresorbed with little new bone with in the defect at 12 weeks. CONCLUSIONS: The utilization of a demineralized bone matrix putty appeared to allow for complete closure of critical sized calvarial defects in New Zealand white rabbits with viable new bone at 12 weeks.     

Trans oral approach to the nasopharynx and clivus using the Le Fort I osteotomy with midpalatal split

The Le Fort I level osteotomy is a procedure well known to oral and maxillofacial surgeons, who routinely use it to correct midfacial skeletal deformities and alter the dental occlusion. This osteotomy can also be used as a maxillotomy for access to more superiorly and posteriorly situated structures. The downfracture technique provides the surgeon with a safe approach that allows visualization of the maxillary sinuses, nasal cavity, nasopharynx, base of the skull and upper cervical spine. This approach can also be combined with a midline lip split, mandibulotomy and glossotomy to give access to retropharyngeal structures. By modifying the combined Le Fort I and transmandibular approach utilizing a midline split of the hard and soft palate, the access to the clivus can be improved considerably. The clinical applications of these combined procedures in the treatment of basilar invagination and tumors of the nasopharynx are discussed.     

Pin1 regulates TGF-beta1 production by activated human and murine eosinophils and contributes to allergic lung fibrosis

Eosinophilic inflammation is a cornerstone of chronic asthma that often culminates in subepithelial fibrosis with variable airway obstruction. Pulmonary eosinophils (Eos) are a predominant source of TGF-beta1, which drives fibroblast proliferation and extracellular matrix deposition. We investigated the regulation of TGF-beta1 and show here that the peptidyl-prolyl isomerase (PPIase) Pin1 promoted the stability of TGF-beta1 mRNA in human Eos. In addition, Pin1 regulated cytokine production by both in vitro and in vivo activated human Eos. We found that Pin1 interacted with both PKC-alpha and protein phosphatase 2A, which together control Pin1 isomerase activity. Pharmacologic blockade of Pin1 in a rat asthma model selectively reduced eosinophilic pulmonary inflammation, TGF-beta1 and collagen expression, and airway remodeling. Furthermore, chronically challenged Pin1(-/-) mice showed reduced peribronchiolar collagen deposition compared with wild-type controls. These data suggest that pharmacologic suppression of Pin1 may be a novel therapeutic option to prevent airway fibrosis in individuals with chronic asthma.     

Disparities and relative risk ratio of preterm birth in six Central and Eastern European centers

Aim

To identify characteristic risk factors of preterm birth in Central and Eastern Europe and explore the differences from other developed countries.

Method

Data on 33 794 term and 3867 preterm births (<37 wks.) were extracted in a retrospective study between January 1, 2007 and December 31, 2009. The study took place in 6 centers in 5 countries: Czech Republic, Hungary (two centers), Romania, Slovakia, and Ukraine. Data on historical risk factors, pregnancy complications, and special testing were gathered. Preterm birth frequencies and relevant risk factors were analyzed using Statistical Analysis System (SAS) software.

Results

All the factors selected for study (history of smoking, diabetes, chronic hypertension, current diabetes, preeclampsia, progesterone use, current smoking, body mass index, iron use and anemia during pregnancy), except the history of diabetes were predictive of preterm birth across all participating European centers. Preterm birth was at least 2.4 times more likely with smoking (history or current), three times more likely with preeclampsia, 2.9 times more likely with hypertension after adjusting for other covariates. It had inverse relationship with the significant predictor body mass index, with adjusted risk ratio of 0.8 to 1.0 in three sites. Iron use and anemia, though significant predictors of preterm birth, indicated mixed patterns for relative risk ratio.

Conclusion

Smoking, preeclampsia, hypertension and body mass index seem to be the foremost risk factors of preterm birth. Implications of these factors could be beneficial for design and implementation of interventions and improve the birth outcome.Preterm birth (PTB: spontaneous and indicated), defined as delivery before 37 weeks of gestation, is the most common cause of neonatal mortality in developed countries (1). Worldwide, prematurity complications are the most common cause of neonatal deaths (2), accounting for 80% of the world’s 1.1 million deaths (3,4). Fetal, neonatal, and infant mortality rates vary widely between the countries of Europe. Preterm babies born before 28 weeks of gestational age constitute over one-third of all deaths, but data are not comparable between countries (5).Children born prematurely have a higher incidence of cerebral palsy, sensory deficits, respiratory illnesses, and learning disabilities compared to children born at term. The morbidity associated with preterm birth often extends to later life, resulting in enormous physical, psychological, and economic costs (6,7).In developing countries, accurate and complete population data and medical records often do not exist. Therefore, few international studies regarding preterm birth and neonatal deaths have compared social, economic, or ethnic differences, even though several potential risk factors for preterm birth have been identified, including race, physical environment, nutrition, socioeconomic status, and reproductive age (1,8). Maternal height and weight may also contribute to PTB (9-12), along with cigarette smoking or illicit drug use (13,14). In addition, maternal iron, folic acid, and vitamin D deficiencies may increase the risk for preterm delivery, with nutritional differences among ethnic groups likely contributing to disparities in prematurity (15).The contribution of specific risk factors for PTB in Central and Eastern European counties is unknown. Therefore, the Mother and Child Health Research Network (M&CH RN), as one of the networks of the Association for Regional Cooperation in Health, Science and Technology (RECOOP HST), instituted a retrospective review of delivery records of participating hospitals to identify the risk factors of preterm birth. Its specific aims were to identify the risk factors of preterm birth specific for Central and Eastern Europe (CEE).     

Immune cell trafficking to the islets during type 1 diabetes

Inhibition of immune cell trafficking to the pancreatic islets during type 1 diabetes (T1D) has therapeutic potential, since targeting of T cell and B cell trafficking has been clinically effective in other autoimmune diseases. Trafficking to the islets is characterized by redundancy in adhesion molecule and chemokine usage, which has not enabled effective targeting to date. Additionally, cognate antigen is not consistently required for T cell entry into the islets throughout the progression of disease. However, myeloid cells are required to enable T cell and B cell entry into the islets, and may serve as a convergence point in the pathways controlling this process. In this review we describe current knowledge of the factors that mediate immune cell trafficking to pancreatic islets during T1D progression.     

Echocardiographic Doppler assessment of the biophysical properties of the aorta in pediatric patients with the Marfan syndrome

In the Marfan syndrome (MS), aortic root involvement is usually clinically monitored according to the aortic sinus of Valsalva dilation. Using an echocardiographic Doppler method in this cross-sectional study, abnormal biophysical properties of the ascending aorta were found in pediatric patients with MS compared with healthy controls but not consistently in association with the aortic sinus of Valsalva dilation.