Experimental amine-epoxide sealer: a physicochemical study in comparison with AH Plus and EasySeal.

AIM: To compare selected physicochemical and biological properties of an experimental sealer with those of two commercially available sealers. METHODOLOGY: AH Plus and EasySeal were used as model materials for commercially available amine-epoxide sealers. They were mixed as stated by the manufacturer. The two components of experimental sealer EvoSeal A were mixed 1 : 1 vol%. The setting time was determined in two different ways: first, by setting of sealers in a temperature- and moisture-controlled environment followed by testing with a Gilmore needle and secondly, by oscillating measurements of setting behaviour using a rheometer. Differential scanning calorimetry (DSC) of the sealer was performed for comparison of thermal properties. Flow and film thickness were determined by applying pressures of 100 g and 15.3 kg, respectively, on the materials between two glass plates and measuring the diameters of the compressed sealer and the thickness with a micrometer gauge. Solubility of set materials was conducted by layering the samples with water, storing in a temperature- and humidity-controlled environment and evaporating the solvent. The solved sealer parts were then weighed. The radiopacity was measured in an X-ray experiment comparing radiopacity of a cured sealer to an aluminium step wedge. Volume shrinkage was defined by measuring the densities of samples before and after setting. The film thickness, fluidity, curing time, radiopacity and solubility of the test materials were performed as specified in DIN EN ISO 6876:2010 draft. The volume shrinkage was determined in a method adapted from standard DIN 13907:2007-01. Antibacterial activity was tested against Gram-positive Streptococcus oralis cultures in a contact test based on standard ISO 22196:2011 (E). Statistical analysis was performed using Mann-Whitney U-test where applicable. Significant differences were determined with P < 0.05. RESULTS: The experimental sealer, EvoSeal A, reached standard specifications. In terms of film thickness, the highest value was measured for EvoSeal A with a film thickness of 27 µm, comparing to 6 µm for EasySeal (P ≤ 0.001) and 8 µm for AH Plus (P ≤ 0.001). Comparing the flow, all values corresponded to EasySeal with a diameter of 17.3 mm. The only significant difference was determined for AH Plus compared to EvoSeal A (P = 0.0353). Volume shrinkage of EvoSeal A was 48% smaller compared to EasySeal and approximately 20% lower compared to AH Plus. The shortest curing time was determined for EvoSeal A (3.0 h) followed by EasySeal (4.1 h) and AH Plus (24 h). For all groups, significant differences were observed (P ≤ 0.001). EvoSeal A had a significantly higher radiopacity than EasySeal (P ≤ 0.001) but significantly lower values than AH Plus (P ≤ 0.001). The solubility of AH Plus and EvoSeal A was <0.5% (P = 0.2435). Compared to EasySeal with a solubility of 2.7%, significant differences were observed (P ≤ 0.02). Three weeks after setting, EasySeal and EvoSeal A still had an antibacterial effect against S. oralis in contrast to AH Plus. In this respect, comparing AH Plus with EvoSeal A and EasySeal, respectively, significant differences were observed (P ≤ 0.001). No significant differences between EasySeal with EvoSeal A (P = 0.540) were determined. CONCLUSIONS: The physical and chemical properties of the experimental sealer EvoSeal A were comparable to the two commercially established sealers EasySeal and AH Plus.

Accessing targeted nanoparticles to the brain: the vascular route.

The blood-brain barrier (BBB), formed by brain capillary endothelial cells, prevents the entry of several drug molecules to the brain, especially molecules hydrophilic in nature. Advanced drug carriers like nanoparticles share the potential to allow entry of therapeutic proteins and genetic molecules into the central nervous system (CNS). Taking a targeting approach by conjugating molecules acting as ligands or monoclonal antibodies with affinity for proteins expressed on the luminal side of brain capillary endothelial cells, the nanoparticles can be designed to enable transport into the brain endothelium, or perhaps even through the endothelium leading to blood to brain transport. Currently, the iron-binding protein transferrin or antibodies raised against the transferrin receptor denote the most feasible molecule for targeting purposes at the BBB. This manuscript reviews the targetability of nanoparticles to the brain capillary endothelial cells, how nanocarriers may enter and transfer through the brain endothelium, and how likely restraints denoted by the threedimensional mesh of the extracellular proteins forming the brain capillary basement membrane challenge the possibilities for enabling transport of large molecules through the BBB encapsulated in nanoparticles.

Development of a predictive model for estimating the probability of treatment success one year after total shoulder replacement - cohort study.

OBJECTIVE: To Estimate the probability of treatment success 1 year after a total shoulder arthroplasty by developing a model based on preoperative clinical factors. METHOD: Between June 2003 and December 2006, 140 patients undergoing shoulder operations were assessed for age, gender, current rheumatoid arthritis, Short Form (SF) 36 physical and mental sum scores, previous shoulder operations, the Disabilities of Arm, Shoulder and Hand (DASH) symptom and function scores, the Shoulder Pain and Disability Index (SPADI), and insurance status. One year after the operation a Constant score of 80 or more out of 100 indicated successful treatment. Patient variables were analyzed with a logistic regression model augmented in a stepwise manner and bootstrapped 100 times. Variables selected at least 33 times were incorporated into a final model and the Area under the Receiver Operating Characteristics Curve (aROC) was calculated. RESULTS: There were 47/140 (33.6%) successful treatments. The probability of success was reduced in patients with previous shoulder operations (Odds Ratio [O.R.] 0.17, 95% Confidence Interval (95%CI) 0.04-0.85; P=0.03) and older than 75 years (O.R. 0.21, 95%CI 0.05-0.77; P=0.02). The probability of success increased in patients with a higher SF 36 mental sum score (O.R. 1.03, 95%CI 0.96-1.09, P=0.42) and a higher DASH function score (O.R. 1.05, 95%CI 1.02-1.07, P=0.001). The aROC was 0.79 (0.70-0.88) indicating that the model has a high predictive capacity. CONCLUSION: Once validated this model based on four preoperative clinical factors offers a prediction of whether a patient will respond to treatment 1 year after total shoulder arthroplasty.

[MR imaging of variants of the superior labral-bicipital complex and SLAP lesions]. / Normvarianten des oberen Labrum-Bizepssehnen-Komplexes und differentialdiagnostische Kriterien von SLAP-Läsionen in der Magnetresonanztomographie.

In the detection of SLAP (superior labral anterior to posterior) lesions of the shoulder MR arthrography shows a significantly higher sensitivity compared with conventional MR techniques and therefore, represents the method of choice in diagnostic imaging of the superior labral-bicipital complex. On the basis of morphological criteria it mostly allows distinction of traumatic lesions and anatomic variants of the superior labrum and the biceps anchor as well as classification of detected SLAP lesions (types 1-4 according to Snyder). However, the differentiation of a SLAP type 2 lesion and a sublabral recess can be very difficult, even if all distinction criteria are considered.

Neonatal outcome when delivery follows a borderline immature lecithin to sphingomyelin ratio.

OBJECTIVE: Occasionally, clinicians are presented with a complicated preterm pregnancy where fetal pulmonary maturity testing might be used to help guide management decisions. However, should delivery be allowed if the lecithin to sphingomyelin ratio (L/S ratio) is not quite mature? The incidence of newborn complications after delivery with L/S ratio values of 1.8 and 1.9 is unknown. The purpose of this study was to evaluate the neonatal morbidity and mortality in patients that delivered with these borderline immature results. STUDY DESIGN: All patients who underwent fetal pulmonary maturity testing were prospectively recorded in log books. An L/S ratio of > or = 2.0 was considered mature. Patients with an L/S ratio of 1.8 or 1.9 were considered "borderline immature." These borderline immature cases were evaluated for the gestational age at amniocentesis, the gestational age at delivery, and neonatal outcome. RESULTS: During the 9-year study period, L/S ratio testing was performed on 2038 patients. Of these, 162 preterm patients (7.9%) had an L/S ratio of 1.8 or 1.9 A total of 63 of these 162 patients delivered < 72 hours after the amniocentesis and met study criteria. The pregnancies ranged from 27 to 36 weeks' gestation. There was a 13% incidence (95% confidence interval (CI) of 4% to 30%) of major neonatal morbidity and a 3% incidence (95% CI of 0% to 17%) of neonatal mortality in the 30 pregnancies with an L/S ratio of 1.8. The incidence of major neonatal morbidity was only 3% (95% CI of 0% to 15%) in the 33 patients with an L/S ratio of 1.9, with no cases of mortality (95% CI of 0% to 9%). CONCLUSION: Based on 95% CIs, the data of this study reveal that the maximum risk for major morbidity is < or = 15%, with a mortality risk of < 10% in a preterm newborn delivered with a 1.9 L/S ratio value. The maximum risk is 30% for major morbidity and 17% for mortality in preterm newborns delivered with a 1.8 L/S ratio. This information may help in the decision-making process of whether to deliver or to observe when faced with a borderline immature L/S ratio result in a complicated preterm pregnancy.

Immunohistochemical distribution of serotonin in spinal autonomic nuclei: II. Early and late postnatal ontogeny in the rat.

These studies reveal that the postnatal ontogeny of serotonin (5HT) in the sympathetic nuclei of the rat spinal cord is protracted; the adult complement of 5HT-immunoreactive fibers is not achieved until at least 60 days of age. As descending serotonin fibers innervate and demarcate the distribution of preganglionic sympathetic nuclei, rostral-caudal and temporal gradients exist. Additionally, a heterogeneous segmental 5HT ontogenetic pattern is observed in sympathetic nuclei. Most serotonin fibers in laminae VII and X are unorganized at birth except for some sympathetic nuclei in high thoracic regions where the 5HT sympathetic pattern is being initiated. By postnatal day 6 the framework of the 5HT pattern is established in all sympathetic nuclei, and by postnatal day 16 a pattern is formed, which develops into the compact adult state by postnatal day 60. The protracted period of sympathetic 5HT development corresponds with the length of time it takes for the autonomic nervous system to mature. In addition, 5HT intraspinal cell bodies are observed at all time points examined, except for the day of birth, and are found in the same regions as adult 5HT neurons, i.e., dorsal or lateral to the central canal in laminae VII and X and in all spinal segments except cervical levels. Many of the 5HT neurons are pericanalicular and bipolar in appearance. Multipolar 5HT neurons are first observed on postnatal day 45.

The postnatal ontogeny of substance P-immunoreactive fibers in the sympathetic preganglionic nuclei of the rat.

The ontogeny of substance P (SP)-containing fibers and puncta is described in laminae VII and X of the rat thoracolumbar spinal cord from the day of birth until postnatal day (P) 60. As SP fibers and puncta innervate and demarcate the distribution of preganglionic sympathetic nuclei, strong temporal and weak rostrocaudal ontogenetic gradients exist. Additionally, a heterogeneous segmental SP ontogenetic pattern is observed in sympathetic nuclei. On the day of birth, SP fibers are present in an unorganized fashion in sympathetic nuclei with the exception of the nucleus intercalatus which is clearly outlined. From P0 to P4 SP fibers and puncta are established along a 'ladder-like' pattern and from P6 to P15 SP fibers and puncta steadily accumulate in sympathetic nuclei at all spinal levels. By P15 the nuclei intermediolateralis, pars principalis and funicularis, and the nucleus intercalatus are clearly outlined by SP immunoreactivity while the central autonomic region (lamina X) contains heterogeneous bands of SP immunoreactivity. From P20 to P30, SP fibers and puncta accumulate in each autonomic nucleus and longitudinal SP connections form between each adjacent nucleus intermediolateralis pars principalis. Along the spinal midline the nucleus intercalatus pars paraependymalis and the dorsal commissural nucleus emerge from the central autonomic region as separate SP-innervated nuclei. On P40 a period of reorganization takes place so that SP fibers within sympathetic nuclei become more diffuse and the nucleus intercalatus becomes more complex in appearance. The adult SP pattern is formed by P60 when the dorsal commissural nucleus dense core becomes the last autonomic region to be SP innervated. In addition, a transient population of immunohistochemically demonstrable cervical-thoracic laminae VII and X SP cell bodies are observed from P2 to P15.

[Relationships between effects and plasma levels of clozapine (author's transl)]. / Beziehungen zwischen Wirkungen und Plasmaspiegeln von Clozapin.

Relations between clozapine plasma levels and effects were investigated in 32 hospitalized patients. Clozapine dosage and plasma levels correlate linearly. The clinical improvement due to clozapine treatment was significant. A relationship between the rate of improvement and the plasma levels could be seen on the third day of treatment only. Of the side effects, body temperature elevation and orthostatic disregulation temporarily correlated with the plasma levels. Development of tolerance was seen with regard to the sedative effect and orthostatic disregulation. Linear correlations between pulse frequency as well as dopamine-beta-hydroxylase activity in serum and clinical improvement were observed during the second half of the 30-day treatment period.

[Antipsychotic efficacy in relation to plasma levels of clozapine (author's transl)]. / Antipsychotische Wirksamkeit im Verhältnis zum Plasmaspiegel von Clozapin

The relationship between antipsychotic effect and side effects and plasma levels of clozapine were investigated in 26 patients. A significant linear correlation was found between dosage and plasma levels of clozapine. All patients were clearly improved. The degree of improvement was independent of the plasma levels in an average range of plasma levels (100 ng/ml-800 ng/ml). Sedation and orthostatic dysregulation occurred most pronounced on the third day of treatment. There was no relationship between plasma levels and these symptoms. After prolonged treatment the degree of both symptoms diminished. The development of tolerance of symptoms is concluded.