Mice Mutated in the First Fibronectin Domain of Adhesion Molecule L1 Show Brain Malformations and Behavioral Abnormalities.

The X-chromosome-linked cell adhesion molecule L1 (L1CAM), a glycoprotein mainly expressed by neurons in the central and peripheral nervous systems, has been implicated in many neural processes, including neuronal migration and survival, neuritogenesis, synapse formation, synaptic plasticity and regeneration. L1 consists of extracellular, transmembrane and cytoplasmic domains. Proteolytic cleavage of L1's extracellular and transmembrane domains by different proteases generates several L1 fragments with different functions. We found that myelin basic protein (MBP) cleaves L1's extracellular domain, leading to enhanced neuritogenesis and neuronal survival in vitro. To investigate in vivo the importance of the MBP-generated 70 kDa fragment (L1-70), we generated mice with an arginine to alanine substitution at position 687 (L1/687), thereby disrupting L1's MBP cleavage site and obliterating L1-70. Young adult L1/687 males showed normal anxiety and circadian rhythm activities but enhanced locomotion, while females showed altered social interactions. Older L1/687 males were impaired in motor coordination. Furthermore, L1/687 male and female mice had a larger hippocampus, with more neurons in the dentate gyrus and more proliferating cells in the subgranular layer, while the thickness of the corpus callosum and the size of lateral ventricles were normal. In summary, subtle mutant morphological changes result in subtle behavioral changes.

CHL1 depletion affects dopamine receptor D2-dependent modulation of mouse behavior.

Introduction: The dopaminergic system plays a key role in the appropriate functioning of the central nervous system, where it is essential for emotional balance, arousal, reward, and motor control. The cell adhesion molecule close homolog of L1 (CHL1) contributes to dopaminergic system development, and CHL1 and the dopamine receptor D2 (D2R) are associated with mental disorders like schizophrenia, addiction, autism spectrum disorder and depression. Methods: Here, we investigated how the interplay between CHL1 and D2R affects the behavior of young adult male and female wild-type (CHL+/+) and CHL1-deficient (CHL1-/-) mice, when D2R agonist quinpirole and antagonist sulpiride are applied. Results: Low doses of quinpirole (0.02 mg/kg body weight) induced hypolocomotion of CHL1+/+ and CHL1-/- males and females, but led to a delayed response in CHL1-/- mice. Sulpiride (1 mg/kg body weight) affected locomotion of CHL1-/- females and social interaction of CHL1+/+ females as well as social interactions of CHL1-/- and CHL1+/+ males. Quinpirole increased novelty-seeking behavior of CHL1-/- males compared to CHL1+/+ males. Vehicle-treated CHL1-/- males and females showed enhanced working memory and reduced stress-related behavior. Discussion: We propose that CHL1 regulates D2R-dependent functions in vivo. Deficiency of CHL1 leads to abnormal locomotor activity and emotionality, and to sex-dependent behavioral differences.

Mice Mutated in the Third Fibronectin Domain of L1 Show Enhanced Hippocampal Neuronal Cell Death, Astrogliosis and Alterations in Behavior.

Adhesion molecules play major roles in cell proliferation, migration, survival, neurite outgrowth and synapse formation during nervous system development and in adulthood. The neural cell adhesion molecule L1 contributes to these functions during development and in synapse formation and synaptic plasticity after trauma in adulthood. Mutations of L1 in humans result in L1 syndrome, which is associated with mild-to-severe brain malformations and mental disabilities. Furthermore, mutations in the extracellular domain were shown to cause a severe phenotype more often than mutations in the intracellular domain. To explore the outcome of a mutation in the extracellular domain, we generated mice with disruption of the dibasic sequences RK and KR that localize to position 858RKHSKR863 in the third fibronectin type III domain of murine L1. These mice exhibit alterations in exploratory behavior and enhanced marble burying activity. Mutant mice display higher numbers of caspase 3-positive neurons, a reduced number of principle neurons in the hippocampus, and an enhanced number of glial cells. Experiments suggest that disruption of the dibasic sequence in L1 results in subtle impairments in brain structure and functions leading to obsessive-like behavior in males and reduced anxiety in females.

Myosin XVI Regulates Actin Cytoskeleton Dynamics in Dendritic Spines of Purkinje Cells and Affects Presynaptic Organization.

The actin cytoskeleton is crucial for function and morphology of neuronal synapses. Moreover, altered regulation of the neuronal actin cytoskeleton has been implicated in neuropsychiatric diseases such as autism spectrum disorder (ASD). Myosin XVI is a neuronally expressed unconventional myosin known to bind the WAVE regulatory complex (WRC), a regulator of filamentous actin (F-actin) polymerization. Notably, the gene encoding the myosin's heavy chain (MYO16) shows genetic association with neuropsychiatric disorders including ASD. Here, we investigated whether myosin XVI plays a role for actin cytoskeleton regulation in the dendritic spines of cerebellar Purkinje cells (PCs), a neuronal cell type crucial for motor learning, social cognition and vocalization. We provide evidence that both myosin XVI and the WRC component WAVE1 localize to PC spines. Fluorescence recovery after photobleaching (FRAP) analysis of GFP-actin in cultured PCs shows that Myo16 knockout as well as PC-specific Myo16 knockdown, lead to faster F-actin turnover in the dendritic spines of PCs. We also detect accelerated F-actin turnover upon interference with the WRC, and upon inhibition of Arp2/3 that drives formation of branched F-actin downstream of the WRC. In contrast, inhibition of formins that are responsible for polymerization of linear actin filaments does not cause faster F-actin turnover. Together, our data establish myosin XVI as a regulator of the postsynaptic actin cytoskeleton and suggest that it is an upstream activator of the WRC-Arp2/3 pathway in PC spines. Furthermore, ultra-structural and electrophysiological analyses of Myo16 knockout cerebellum reveals the presence of reduced numbers of synaptic vesicles at presynaptic terminals in the absence of the myosin. Therefore, we here define myosin XVI as an F-actin regulator important for presynaptic organization in the cerebellum.

NT-proBNP is not elevated in patients with obstructive sleep apnoea.

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-ProBNP) has emerged as an important marker of cardiac stress and may reflect the severity of underlying cardiac dysfunction, which is thought to be associated with obstructive sleep apnoea syndrome (OSAS). METHODS: This study evaluated the plasma concentration of NT-ProBNP in 60 consecutive patients (median age 55.7 years, median body mass index (BMI) 31.8) who were referred to a sleep laboratory with a suspicion of OSAS. Each subject underwent measurement of morning NT-ProBNP plasma levels, polysomnography and echocardiography. Patients were treated with nasal continuous or bilevel positive airway pressure ventilation (nCPAP/BIPAP) or without mechanical respiratory support, depending on clinical symptoms and results of polysomnography. Three months after treatment of OSAS 28 of the patients were reassessed for re-evaluation of NT-ProBNP and polysomnography. RESULTS: Low or high levels of NT-proBNP were not associated with AHI and other sleep related indices (p>0.3). There was no correlation between NT-proBNP and AHI or other sleep related indices. In multiple regression analysis, NT-proBNP was significantly correlated with left ventricular ejection fraction, creatinine clearance and the presence of systemic arterial hypertension but not with AHI. CONCLUSIONS: Our results show by a robust multiple regression analysis, that NT-pro BNP is not associated with OSAS and NT-pro BNP cannot be used as a sensitive marker for underlying cardiovascular abnormalities in patients with OSAS.

Pulmonary nodule detection with digital projection radiography: an ex-vivo study on increased latitude post-processing.

To evaluate increased image latitude post-processing of digital projection radiograms for the detection of pulmonary nodules. 20 porcine lungs were inflated inside a chest phantom, prepared with 280 solid nodules of 4-8 mm in diameter and examined with direct radiography (3.0x2.5 k detector, 125 kVp, 4 mAs). Nodule position and size were documented by CT controls and dissection. Four intact lungs served as negative controls. Image post-processing included standard tone scales and increased latitude with detail contrast enhancement (log-factors 1.0, 1.5 and 2.0). 1280 sub-images (512x512 pixel) were centred on nodules or controls, behind the diaphragm and over free parenchyma, randomized and presented to six readers. Confidence in the decision was recorded with a scale of 0-100%. Sensitivity and specificity for nodules behind the diaphragm were 0.87/0.97 at standard tone scale and 0.92/0.92 with increased latitude (log factor 2.0). The fraction of "not diagnostic" readings was reduced (from 208/1920 to 52/1920). As an indicator of increased detection confidence, the median of the ratings behind the diaphragm approached 100 and 0, respectively, and the inter-quartile width decreased (controls: p<0.001, nodules: p=0.239) at higher image latitude. Above the diaphragm, accuracy and detection confidence remained unchanged. Here, the sensitivity for nodules was 0.94 with a specificity from 0.96 to 0.97 (all p>0.05). Increased latitude post-processing has minimal effects on the overall accuracy, but improves the detection confidence for sub-centimeter nodules in the posterior recesses of the lung.

Predictors of gallstone composition in 1025 symptomatic gallstones from Northern Germany.

BACKGROUND: Gallstones represent a prevalent and costly health problem. The changing epidemiology and the emerging non-surgical interventions for gallstone disease necessitate the definition of target populations for future therapies. This study aimed to define patterns of gallstone composition and identify demographic predictors of gallstone composition in a large sample of symptomatic gallstones from Northern Germany. METHODS: One thousand and seventy-four post-cholecystectomy gallstone specimens were obtained. Demographic and clinical information was provided by questionnaire (N = 1025 independent individuals with complete information). Two samples from each gallstone were analyzed using Fourier transformed infrared spectrometry. RESULTS: The most prevalent substance was cholesterol, which was detected in 95.0% of gallstone specimens. Bilirubin and bilirubinate were present in 30.0% and calcium was detected in 10.0% of the spectra. Ninety-two percent of measurements from the same stone yielded the same "main" substances, indicating a homogenous stone composition in most cases. Female sex and higher body mass index (BMI) were associated with the presence of cholesterol as a main substance in the gallstones (p < 0.001). CONCLUSION: The changing epidemiology of gallstone disease is reflected by a marked shift in stone composition: Only two percent of stones in this study were pigment stones as compared to 91% percent of stones containing cholesterol as a main substance. Obese individuals from Germany with a BMI > 30 kg/m2 have in 95% cholesterol-dominant gallstones and represent a potential target population for non-surgical interventions for the prevention or treatment of cholesterol stones.

Survival rate of endodontically treated teeth with posts after prosthetic restoration.

The purpose of this retrospective clinical study was to evaluate the survival rate of teeth that were endodontically treated and restored with endodontic posts and prosthodontic restorations. A total of 864 teeth in 360 patients were included in the study. Dental records and radiographs of the patients were evaluated and four parameters were documented. The parameters were type of post, type of prosthodontic restoration, observation time, and, in cases of failure, failure mode. Statistical survival analyses were performed according to Kaplan-Meier. The mean observation time was 22.5 +/- 14.9 months. The calculated survival rates of the abutments were statistically significant different for fixed partial dentures (FPDs) and for removable partial dentures (RPDs) with survival rates of 92.7% and 51.0% after 60 months, respectively. Most of the presumed factors influencing the survival rate of endodontically treated abutment teeth only affected the outcome in the RPD group. Teeth restored with post and cores present a high risk for failure when used as abutments for conical-double-crown-retained RPDs.

Detection of diverse bacterial signatures in atherosclerotic lesions of patients with coronary heart disease.

BACKGROUND: Bacterial infection has been discussed as a potential etiologic factor in the pathophysiology of coronary heart disease (CHD). This study analyzes molecular phylogenies to systematically explore the presence, frequency, and diversity of bacteria in atherosclerotic lesions in patients with CHD. METHODS AND RESULTS: We investigated 16S rDNA signatures in atherosclerotic tissue obtained through catheter-based atherectomy of 38 patients with CHD, control material from postmortem patients (n=15), and heart-beating organ donors (n=11) using clone libraries, denaturating gradient gel analysis, and fluorescence in situ hybridization. Bacterial DNA was found in all CHD patients by conserved PCR but not in control material or in any of the normal/unaffected coronary arteries. Presence of bacteria in atherosclerotic lesions was confirmed by fluorescence in situ hybridization. A high overall bacterial diversity of >50 different species, among them Staphylococcus species, Proteus vulgaris, Klebsiella pneumoniae, and Streptococcus species, was demonstrated in >1500 clones from a combined library and confirmed by denaturating gradient gel analysis. Mean bacterial diversity in atheromas was high, with a score of 12.33+/-3.81 (range, 5 to 22). A specific PCR detected Chlamydia species in 51.5% of CHD patients. CONCLUSIONS: Detection of a broad variety of molecular signatures in all CHD specimens suggests that diverse bacterial colonization may be more important than a single pathogen. Our observation does not allow us to conclude that bacteria are the causative agent in the etiopathogenesis of CHD. However, bacterial agents could have secondarily colonized atheromatous lesions and could act as an additional factor accelerating disease progression.

Fracture load of composite resin and feldspathic all-ceramic CAD/CAM crowns.

STATEMENT OF PROBLEM: Various machinable materials are currently used with computer-aided design/computer-assisted manufacturing (CAD/CAM) technologies for the chairside fabrication of restorations. However, properties of these new machinable materials, such as fracture load, wear, marginal deterioration, and color stability, should be investigated in vitro under replicated clinical conditions prior to time-consuming clinical studies. PURPOSE: This study investigated the effect of cyclic loading fatigue and different luting agents under wet conditions on the fracture load of CAD/CAM machined composite resin and all-ceramic crowns. MATERIALS AND METHODS: Ninety-six intact human maxillary premolars were prepared for composite resin and all-ceramic crowns with the following preparation criteria: 6-degree axial taper, 1.5-mm shoulder finish line placed 0.5 mm occlusal to the cemento-enamel junction, 1.5-mm axial reduction, 2-mm occlusal reduction, and 5-mm occluso-gingival height. Sixteen unprepared premolars served as controls. Forty-eight all-ceramic crowns (Vita Mark II) and 48 millable composite resin crowns (MZ100 Block) were fabricated using a CAD/CAM system (Cerec 3). Three luting agents-RelyX ARC (RX), GC Fuji CEM (FC), and zinc phosphate cement (ZP)-were used for cementation (n = 16). After 1-week storage in water, half of the specimens (n=8) in each subgroup were cyclically loaded and thermal cycled under wet conditions for 600,000 masticatory cycles and 3500 thermal cycles (58 degrees C/4 degrees C; dwell time, 60 seconds) in a masticatory simulator; the other half (n = 8) were fractured without cyclic loading. All specimens were loaded in a universal testing machine with a compressive load (N) applied along the long axis of the specimen at a crosshead speed of 1 mm/min until fracture. Fracture loads (N) were recorded for each specimen. Three-way analysis of variance was used to detect the effects of the experimental factors (crown material, luting agent, and loading conditions) on the fracture load. The comparison with the unprepared natural teeth as controls was done by means of t tests (alpha=.05). RESULTS: Analysis of variance revealed a statistically significant influence of the luting agent and the cyclic loading (P < .001), whereas the crown material had no significant influence. Cyclic loading fatigue significantly decreased the mean fracture load of test groups independent of the 3 luting agents used: MZ100/ZP, 827.1 to 552.5 N; MZ100/FC, 914.7 to 706.2 N; MZ100/RX, 955.9 to 724.4 N; Vita/ZP, 772.3 to 571.5 N; Vita/FC, 923.6 to 721.1 N; and Vita/RX, 929.1 to 752.7 N. However, there was no significant difference in the mean fracture load of control specimens before and after cyclic loading (1140.1 N and 1066.2 N, respectively). Adhesive luting agents RelyX ARC and GC Fuji CEM increased fracture load significantly compared to zinc phosphate cement. CONCLUSIONS: Cyclic loading fatigue significantly reduced the fracture loads of composite resin and all-ceramic crowns, whereas adhesive cementation significantly increased the fracture loads.

Reproducibility of computer-aided volumetry of artificial small pulmonary nodules in ex vivo porcine lungs.

OBJECTIVE: The main purpose of this study was to investigate the reproducibility of computed tomography (CT)-based volumetric measurements of small pulmonary nodules. METHODS: We implanted 70 artificial pulmonary nodules in 5 ex vivo porcine lungs in a dedicated chest phantom. The lungs were scanned 5 times consecutively with multislice-CT (collimation 16 x 0.75 mm, slice thickness 1 mm, reconstruction increment 0.7 mm). A commercial software package was used for lesion volumetry. The authors differentiated between intrascan reproducibility, interscan reproducibility, and results from semiautomatic and postprocessed volumetry. RESULTS: Analysis of intrascan reproducibility revealed a mean variation coefficient of 6.2% for semiautomatic volumetry and of 0.7% for human adapted volumetry. For interscan reproducibility a mean variation coefficient of 9.2% and for human adapted volumetry a mean of 3.7% was detected. CONCLUSION: The presented volumetry software showed a high reproducibility that can be expected to detect nodule growth with a high degree of certainty.

General well-being as an important co-factor of self-assessment of dental appearance.

PURPOSE: This study aimed to correlate the general well-being of patients and their judgment about their dental appearance. MATERIALS AND METHODS: Based on internationally accepted guidelines regarding dental esthetics, a questionnaire was developed to measure subjective assessments of dental appearance. Fourteen items defined an esthetic sum score (0 = satisfied; 56 = dissatisfied). Further, general well-being was evaluated with a long-established and highly reliable test. Eighty participants were included (47 women, 33 men). Participants were.drawn from 4 different groups (n = 20): natural dentition (group N), fixed partial dentures (group F), removable partial dentures (group R), and patients who had an esthetic problem with their teeth (group P). RESULTS: Seventy-five participants showed a normal well-being. Five participants showed a depressive state and formed a new group (group D). The medians of the sum scores (25th, 75th percentile) were: group N: 12 (10, 14); group F: 14 (8, 29); group R: 14 (9, 27); group P: 23 (18, 35); group D: 30 (26, 35). Significant differences were found between groups N and P, as well as between group D and groups N, F, and R. CONCLUSION: Because of the significant difference between groups N and P, basis validation of the sum score was achieved. Further, self-assessments of dental appearance appeared to be more negative for participants with a depressive state compared with the other groups. In clinical studies, selection bias can be prevented by using a test that measures well-being to verify if a study sample includes a normal number of depressive subjects and therefore represents the general population.

Assessment of dental appearance following changes in incisor proportions.

This study aimed to evaluate the assessment of attractiveness of standardized changes in incisor proportions. Two original photographs, showing the maxillary anterior teeth in the frame of a smile, were computer-manipulated. From the so-produced symmetrical 'golden standard' images, two sets were constructed. Each set contained one golden standard image and seven images with different standardized changes concerning (i) width-to-length ratios of the central incisors (60-96%) and (ii) tooth-to-tooth proportions between the widths of lateral and central incisors (43-87%). The judges, consisting of three groups of individuals (24 dentists, 24 medical students, and 179 patients), ranked each photo set for attractiveness on a visual analogue scale. The width-to-length ratios were assessed as most attractive within a range of 75-85% (medical students, patients) or 75-80% (dentists), respectively. The tooth-to-tooth proportions showed the best results concerning attractive appearance within a range of 50-74% (medical students, patients) or 56-68% (dentists), respectively. No significant differences between the participant groups were found except for some extreme variations. It was concluded that a most attractive 'golden range' could be identified for both the width-to-length ratios and the tooth-to-tooth proportions of the maxillary incisors.

The effect of the topical administration of bioactive glass on inflammatory markers of human experimental gingivitis.

Recent studies demonstrated that bioactive glass attenuated inflammatory reactions and bacterial growth in vitro. The aim of the present clinical study was to evaluate the effects of local bioactive glass-administration in vivo in subjects with experimental gingivitis. In each individual, contralateral teeth served as test and control over a 21-day non-hygiene (preventive phase) and a 7-day therapeutic phase. A 45S5 bioactive glass (10% solution) was applied daily (2 x 1 h) on the test teeth during the preventive and therapeutic phase of the study. Inflammation assessment was based on the plaque index record (PI), on the bleeding frequency (BOP) and the gingival crevicular fluid volume (GCF). Interleukin-1beta levels (IL-1beta) in the GCF were measured by ELISA. Bacterial deposits on teeth increased during the 21-days non-brushing period, with no difference in plaque accumulation between test and control sides. BOP levels were significantly reduced during the therapeutic phase by the application of bioactive glass. GCF-values showed a significant reduction on the test compared to control side during the preventive and therapeutic phase. IL-1beta counts decreased during the last 7 days of the study on the test side, but no significance was given. The topical application of 45S5 bioactive glass in humans with experimental gingivitis attenuated the clinical signs of inflammation, although the bacterial accumulation was not inhibited in this clinical trial.

Plaque removing capacity of a novel high pressure water irrigator.

PURPOSE: To evaluate the capacity of a novel oral water irrigator to remove established plaque deposits. METHODS: The study was designed as a randomized two-treatment, crossover, examiner-blinded clinical trial. The plaque removing capability of a prototype oral irrigator was compared to a conventional electric toothbrush. After 48 hours of plaque accumulation the 35 subjects were randomly assigned to professional plaque removal by either oral irrigation or by electric toothbrushing for a timed 2-minute total cleaning. Pre- and post cleaning plaque was disclosed and gingival abrasions were identified. Plaque was assessed on gingival and approximal surfaces of the oral and buccal sites according to the Rustogi et al modification of the Modified Navy Plaque Index. The assessment of gingival abrasions was performed according to the method introduced by Danser et al. RESULTS: The overall plaque removing capacity of the oral irrigator reached approximately 40.7 +/- 16.7% as compared to 71.6 +/- 11.5% by the electric toothbrush. Similar effects were observed for the gingival and approximal areas. The electric toothbrush caused significantly more gingival abrasions than the oral irrigator.

Assessment of dental appearance following changes in incisor angulation.

PURPOSE: This study evaluated the assessment of attractiveness of standardized changes in incisor angulation of different tooth arrangements. MATERIALS AND METHODS: Four sets of images showing the maxillary anterior teeth without lips against a black background were used for evaluation. Each set contained the original photograph, one computer-manipulated symmetric image, and four images with different standardized changes in incisor angulation (10 degrees). The judges, consisting of three groups (30 dental students, 30 medical students, 30 art students), ranked each photo set for attractiveness from 1 (most attractive) to 6 (most unattractive). RESULTS: The mean ranking (in parentheses) showed that symmetric teeth with ideal axes (2.5) and changes in the angulation of one (2.8) or both (2.5) lateral incisors were significantly more attractive than the angulation of one (4.2) or both (4.6) central incisors. There were no differences between the groups of participants. All findings were reproducible. CONCLUSION: Tooth arrangements showing central incisors with ideal axes were more attractive. Slight changes in the angulation of one or both lateral incisors did not influence attractiveness negatively.

Phosphorylcholine or heparin coating for pediatric extracorporeal circulation causes similar biologic effects in neonates and infants.

OBJECTIVE: Cardiac surgery for complex congenital malformations with use of extracorporeal circulation predisposes to an excessive systemic inflammatory response and a consecutive capillary leak syndrome. In a prospective randomized study the influence of 2 oxygenators especially designed for pediatric use on inflammatory markers and clinical outcome was investigated. METHODS: Forty neonates and infants (body surface area, <0.36 m(2)) undergoing cardiac surgery with extracorporeal circulation were randomized into one of 3 groups: in the first group (n = 14) the Medtronic Minimax Oxygenator and in the second group (n = 12) the Dideco Lilliput 1 Oxygenator, both with a 750-mL priming volume, were used. In the third group the Dideco Lilliput 1 Oxygenator was filled with a reduced priming volume of 450 mL. Parameters of interest for evaluation of a systemic inflammatory response after extracorporeal circulation were interleukin 6, tumor necrosis factor alpha, neutrophil elastase, complement C3, and free hemoglobin. In addition, erythrocyte, leukocyte, and thrombocyte counts and hemoglobin and C-reactive protein values were determined at different measurement points before, during, and after the operation. RESULTS: In all 3 groups peak values for tumor necrosis factor alpha were observed during the operation, whereas interleukin 6, elastase, and free hemoglobin values peaked in the first 4 hours. The highest values for leukocytes and C-reactive protein were obtained between 24 and 72 hours after the operation. Erythrocyte and thrombocyte counts, as well as hemoglobin values, were lowest at extracorporeal circulation onset, normalizing under substitution in the first 4 hours after the operation. By using the Lilliput/750 oxygenator, higher interleukin 6 values 1 and 4 hours after the operation and higher tumor necrosis factor alpha values during and 1 hour after the operation could be observed compared with results with the Minimax and Lilliput/450 oxygenators. In spite of our randomization protocol, patients in the Lilliput/750 group were significantly smaller and younger than those in the Minimax group. However, the statistical analysis showed no correlation between age and interleukin 6 or tumor necrosis factor alpha values, but it did show a correlation between younger age and the occurrence of capillary leak syndrome. Accordingly, the number of children with clinically complicated course (capillary leak, longer duration of catecholamine therapy, and ventilation) was higher in the Lilliput/750 group than in the Minimax group. CONCLUSION: By using an adequate priming volume, the systemic inflammatory response is similar after use of the Dideco Lilliput 1 Oxygenator and the Medtronic Minimax Oxygenator. Tip-to-tip surface coating of the extracorporeal circulation with either heparin or phosphorylcholine seems to have similar biologic effects in neonates and infants undergoing cardiac surgery.

Bone formation in the presence of platelet-rich plasma vs. bone morphogenetic protein-7.

Growth factors contained in platelet-rich plasma (PRP) have recently been proposed to enhance maturation of bone grafts and, in combination with anorganic bovine bone, to support repair in the treatment of small bone defects in maxillofacial surgery. Bone morphogenetic proteins (BMP) carried in a matrix may be able to replace the autologous bone graft in the treatment of critical size defects. However, no studies have compared the bone stimulating capacity of PRP and BMP. Likewise there is no data comparing the effects of PRP in either an autologous bone graft or in anorganic bovine bone. We augmented the mandible of Wistar rats (n = 28) on both sides with either anorganic bovine bone (Bio-Oss) or autologous rib bone. On the test side we applied either 20 microl of autologous PRP or 10 microl of rhBMP-7 (4 groups, n = 7). In addition, bone induction was evaluated in an extraskeletal site (n = 14). A polychrome sequential labeling was performed. The animals were sacrificed by intra-vital perfusion on day 50. Undecalcified ground sections were evaluated by microradiography, digitized histomorphometry and under fluorescent light. The qualitative analysis of fluorochrome labels suggested that PRP and rhBMP-7 accelerated bone growth. However, histomorphometric analysis revealed no significant differences in the area of newly mineralized bone under either the influence of PRP or rhBMP-7 on autologous bone graft. Likewise, the addition of PRP to anorganic bovine bone showed no statistical difference to the control group. The strongest bone stimulating effect was seen for the combination of rhBMP-7 with anorganic bovine bone (p = 0.028). In the extraskeletal model, newly formed bone was evident in the presence of rhBMP-7, but not of PRP. In conclusion, according to the histomorphometry, the addition of platelet-rich plasma failed to enhance bone formation on anorganic bovine bone and on autologous bone grafts.

A recurrent gain of chromosome arm 3q in primary squamous carcinoma of the vagina.

Primary carcinomas of the vagina are rare tumors, accounting for 2%-3% of all gynecologic malignancies. Only a few karyotypes based on chromosome banding techniques have been reported. We have, therefore, used comparative genomic hybridization to establish a pattern of genomic imbalances in vaginal squamous cell carcinomas. Analysis of 16 formalin-fixed and paraffin-embedded tumors revealed that 70% of vaginal carcinomas carry relative copy number increases that map to chromosome arm 3q. Other recurring gains were observed on chromosome arms 5p and 19p. Chromosomal losses were infrequent. Most tumors were aneuploid, as measured by image cytometry on Feulgen-stained tissue sections. The cytogenetic data were related to the presence of human papillomavirus genomes, expression of laminin-5 as a marker for invasiveness, and expression levels of markers for proliferative activity and mutated TP53. All relevant clinical data were recorded. The results suggest that vaginal carcinomas are defined by a specific distribution of chromosomal aneuploidies and that the pattern of genomic imbalances is strikingly similar to that observed in squamous cell carcinomas of the uterine cervix. Age at diagnosis (P=0.031), tumor size (P=0.025), and increased laminin-5 expression (P=0.006) have a significant influence on the survival time.

Behavioral alterations in mice deficient for the extracellular matrix glycoprotein tenascin-R.

We investigated the behavior of mice deficient for the extracellular matrix (ECM) glycoprotein tenascin-R (TN-R) in comparison to their wild-type (WT) littermates. A longitudinal study including tests for exploration and anxiety, motor coordination and cognition was carried out. Mice were tested at different ages, ranging from 3 weeks to 11 months and under different housing conditions. TN-R deficient mice displayed decreased motivation to explore and an increased anxiety profile in the free choice open field (FCOF), open field (OF) and elevated plus maze (EPM) tests. Moreover, the anxiety level of TN-R deficient mice was more strongly influenced by environmental factors as compared to WT littermates. TN-R deficient mice showed motor coordination impairments in the wire hanging, Rotarod and pole test. Thus TN-R ablation leads to an altered behavioral phenotype in mice that may negatively affect their fitness under natural conditions.