[Predictive value of cerebellar growth and general movements assessments for neurodevelopment of very preterm infants at 18-24 months' corrected age]. / Valor pronostico de las evaluaciones del crecimiento cerebelar y de los movimientos generales para el neurodesarrollo del gran prematuro entre los 18 y 24 meses de edad corregida.

INTRODUCTION: Fidgety movements assessments is very sensitive predicting long-term outcome or cerebral palsy of preterm, disrupted cerebellar growth has been reported in these patients. AIM: To compare the predictive value of cerebellar ultrasound growth and fidgety movements assessments, for neurodevelopment outcome of very preterm at 18-24 month's corrected age (CA). SUBJECTS AND METHODS: Prospective study of 88 infants cohort (<= 32 weeks' gestation), transverse cerebellar diameter was obtained by ultrasound via mastoid fontanel, in a weekly basis, until 40 weeks CA. Fidgety movements were assessed at 3 months CA. Neurodevelopment outcome at 18-24 month's CA was evaluated in 68 using Schedule of Growing Skills II Scale (SGS-II) and Amiel-Tison Neurologic Assessment (ATNA). RESULTS: At term age, cerebellar growth was under 3rd percentile in 11 (10.3%). Fidgety movements were normal in 42 (61.8%) and abnormal or absent in 7 (10.3%). At 18-24 months CA, 54 (79.4%) were normal by the SGS-II and in 6 (8.8%) ATNA classified as cerebral palsy. Cerebellar diameter under 3rd percentile at term was associated with abnormal motor outcome and normal fidgety movements correlated with normal neurodevelopment. CONCLUSION: Ultrasound cerebellar measurements and functional examinations (fidgety movements) have important complementary roles in predicting neurodevelopment of very preterm.

TITLE: Valor pronostico de las evaluaciones del crecimiento cerebelar y de los movimientos generales para el neurodesarrollo del gran prematuro entre los 18 y 24 meses de edad corregida.Introduccion. La evaluacion de los movimientos de ajetreo es sumamente sensible a la hora de predecir el desenlace a largo plazo o la paralisis cerebral del neonato prematuro, un tipo de paciente en el que se ha descrito el crecimiento anomalo del cerebelo. Objetivo. Comparar el valor pronostico de la determinacion ecografica del crecimiento anomalo del cerebelo y el de la evaluacion de los movimientos de ajetreo en el neurodesarrollo de grandes prematuros a los 18-24 meses de edad corregida. Sujetos y metodos. Estudio prospectivo con una cohorte de 88 neonatos (32 semanas o menos de gestacion) en que se analizo el diametro transversal del cerebelo por medio de una ecografia semanal hasta las 40 semanas de edad corregida. Los movimientos de ajetreo se evaluaron a los tres meses de edad corregida. El estado de maduracion neurologica a los 18-24 meses de edad corregida se evaluo en 68 neonatos con la escala de evaluacion de las competencias en el desarrollo infantil (SGS-II) y la escala de evaluacion neurologica de Amiel-Tison (ATNA). Resultados. En la edad a termino, el crecimiento del cerebelo fue inferior al tercer percentil en 11 neonatos (10,3%). Los movimientos de ajetreo eran normales en 42 (61,8%), y anormales o ausentes, en 7 (10,3%). A los 18-24 meses de edad corregida, 54 (79,4%) mostraron resultados normales en la SGS-II y 6 (8,8%) fueron calificados como afectados por paralisis cerebral segun la ATNA. El diametro cerebelar inferior al tercer percentil a termino estuvo asociado con un desenlace motor anomalo y los movimientos de ajetreo normales se correlacionaron con el neurodesarrollo normal. Conclusion. La estimacion del tamaño del cerebelo y las exploraciones funcionales (movimientos de ajetreo) poseen un importante papel complementario en el pronostico del desarrollo nervioso en el gran prematuro.

Quality of life and cognitive functions in early onset multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease of the CNS occurring in young adults and even in children in 5% of cases. Lower quality of life (QoL) and cognitive impairment (CI) (40-54%) have been reported in early-onset MS (EO-MS) patients. OBJECTIVE: To assess QoL and cognitive function in EO-MS and their relationship, also considering demographic and clinical variables. METHODS: Paediatric Quality of life inventory Version 4.0 for patients aged 13-18 and 19-25 years, Beck Depression Inventory II (BDI II) and the Rao Brief Repeatable Battery were performed in EO-MS patients (onset age ≤25years). EDSS and MSSS were performed at same time. After testing for normal distribution, group comparisons were performed through the two-tailed Student's t test, one-way analysis of variance (ANOVA) and linear or logistic regression when appropriate. The Bonferroni correction for multiple testing was used when appropriate. RESULTS: 59 patients were included (mean age: 20 ± 3.6; Female sex 52.54%). 34 patients had a paediatric onset (<18 years) while 20 patients had a juvenile onset (18 < age < 25 years) of disease. 5 patients were excluded for missing data. HR-QoL was higher in paediatric than juvenile MS patients (p = 0.02), and it was inversely related to EDSS (p = 0.0005) and Multiple Sclerosis Severity score (MSSS) (p = 0.0001). Sixtyone % of patients showed a CI at BRB. No association was found between CI and any socio-demographic and clinical data. HR-QoL total score was not related to CI status nor to any domain-specific cognitive function score, even considering BDI as possible bias. CI was related to social, physical functioning score and EDSS (p = 0.01) at a logistic regression backward stepwise estimation. CONCLUSION: HR-QoL resulted to be better in paediatric than juvenile MS onset patients and was inversely related to rapidity of disability accumulation, while cognitive impairment was influenced by physical disability and poor social involvement (school, education …). Social participation, affective relations and psychological flexibility could have a protective function on CI.

Synthesis, bioactivity and preliminary biocompatibility studies of glasses in the system CaO-MgO-SiO2-Na2O-P2O5-CaF2.

New compositions of bioactive glasses are proposed in the CaO-MgO-SiO(2)-Na(2)O-P(2)O(5)-CaF(2) system. Mineralization tests with immersion of the investigated glasses in simulated body fluid (SBF) at 37°C showed that the glasses favour the surface formation of hydroxyapatite (HA) from the early stages of the experiments. In the case of daily renewable SBF, monetite (CaHPO(4)) formation competed with the formation of HA. The influence of structural features of the glasses on their mineralization (bioactivity) performance is discussed. Preliminary in vitro experiments with osteoblasts' cell-cultures showed that the glasses are biocompatible and there is no evidence of toxicity. Sintering and devitrification studies of glass powder compacts were also performed. Glass-ceramics with attractive properties were obtained after heat treatment of the glasses at relatively low temperatures (up to 850°C).

Bowel habits in the first 24 months of life: preterm- versus term-born infants.

BACKGROUND AND AIM: New prospective studies concerning feeding and bowel habits of term and preterm infants from birth to 24 months of life are needed. The aim of the present study was to describe and compare feeding and bowel habits between term- and preterm-born infants starting from birth up to the age of 24 months. PATIENTS AND METHODS: Between August and November 2006 all of the infants admitted to an academic and nonacademic neonatal care unit with gestational age 25 to 42 weeks participated in the study. Bowel diaries were recorded 1 and 2 weeks, and 3, 6, 12, and 24 months after birth. Infants with gastrointestinal surgery, neurological diseases, metabolic diseases, or congenital abnormalities were excluded. RESULTS: A total of 199 (126 preterm) infants were eligible; 153 gave consent for participation. Although feeding frequency was higher in the first 3 months in the preterm born, overall feeding frequency decreased between the first 3 follow-up periods (P < 0.001) in both groups. In the first and second week, breast-fed infants had 2.41 more episodes of defecation per week compared with the formula-fed infants (P = 0.017 and P = 0.021, respectively). Higher median (10th percentile-90th percentile) defecation frequency was only found in week 1 in the term compared with the preterm group (24 [9.4-31.6] versus 16 [6.5-31]; P = 0.002). The overall median defecation frequency was 16 (7-30) per week from birth up to the age of 24 months over the total group of participating infants. CONCLUSIONS: Term and preterm infants have a comparable defecation frequency from the second week of life up to the age of 24 months.

Effects of extracellular calcium concentration on the glutamate release by bioactive glass (BG60S) preincubated osteoblasts.

Glutamate released by osteoblasts sharing similarities with its role in neuronal transmission is a very new scientific concept which actually changed the understanding of bone physiology. Since glutamate release is a calcium (Ca(2+))-dependent process and considering that we have previously demonstrated that the dissolution of bioactive glass with 60% of silicon (BG60S) can alter osteoblast Ca(2+)-signaling machinery, we investigated whether BG60S induces glutamate secretion in osteoblasts and whether it requires an increase in intracellular Ca(2+). Here we showed that the extracellular Ca(2+) increase due to BG60S dissolution leads to an intracellular Ca(2+) increase in the osteoblast, through the activation of an inositol 1,4,5-triphosphate receptor (InsP(3)R) and a ryanodine receptor (RyR). Additionally, we also demonstrated that glutamate released by osteoblasts can be profoundly altered by BG60S. The modulation of osteoblast glutamate released by the extracellular Ca(2+) concentration opens a new window in the field of tissue engineering, since many biomaterials used for bone repair are able to increase the extracellular Ca(2+) concentration due to their dissolution products.

Rietveld structure and in vitro analysis on the influence of magnesium in biphasic (hydroxyapatite and beta-tricalcium phosphate) mixtures.

The structure of two different Mg-substituted biphasic (HAP and beta-TCP) mixtures along with the biphasic mixtures without substituted Mg(2+) was investigated using Rietveld refinement technique. The substituted Mg(2+) was found in the beta-TCP phase and its influence on the composition has led to an increase in HAP content of Mg-containing biphasic mixtures when compared with the HAP content detected in pure biphasic mixtures. The refined structural parameters of Ca(10)(PO(4))(6)(OH)(2) and beta-Ca(3)(PO(4))(2) confirmed that all the investigated compositions have crystallized in the corresponding hexagonal (space group P6(3)/m) and rhombohedral (space group R3c) structures. The substitution of lower sized magnesium was found preferentially incorporated at the sixfold-coordinated Ca (5) site of beta-TCP, which is due to the strong Ca (5).O interaction among all the five different Ca sites of beta-Ca(3)(PO(4))(2). The in vitro tests using primary culture of osteoblasts showed that all the tested samples are biocompatible and promising materials for in vivo studies.

VEGF concentration from plasma-activated platelets rich correlates with microvascular density and grading in canine mast cell tumour spontaneous model.

Canine cutaneous mast cell tumour (CMCT) is a common cutaneous tumour in dog, with a higher incidence than in human. CMCT is classified in three subgroups, well and intermediately differentiated (G1 and G2), corresponding to a benign disease, and poorly differentiated (G3), corresponding to a malignant disease, which metastasize to lymph nodes, liver, spleen and bone marrow. In this study, we have evaluated serum (S), platelet-poor plasma (P-PP), plasma-activated platelet rich (P-APR) and cytosol vascular endothelial growth factor (VEGF) concentrations, microvascular density (MVD) and mast cell density (MCD) in a series of 86 CMCTs and we have correlated these parameters with each other, by means of ELISA detection of VEGF and immunohistochemistry. Results show that VEGF level from cytosol P-APR and MVD were significantly higher in G3 CMCTs as compared to G1 or G2 subgroups. Moreover, a significantly strong correlation among VEGF levels from P-PAR and cytosol, MVD and MCD was found in G3 subgroup. Because VEGF levels from P-APR well correlated with MVD and malignancy grade in CMCT, we suggest that VEGF might be secreted from MCs and it may be a suitable surrogate inter-species angiogenetic markers of tumour progression in CMCT. Finally, CMCT seems to be a useful model to study the role of MCs in tumour angiogenesis and inhibition of MCs degranulation or activation might be a new anti-angiogenic strategy worthy to further investigations.

Duration of meconium passage in preterm and term infants.

BACKGROUND: First passage of stool after birth, meconium, is delayed in preterm infants compared to term infants. The difference in duration of meconium passage until transition to normal stools has however never been assessed in preterm and term infants. HYPOTHESIS: Preterm infants have prolonged duration of passage of meconium (PoM) compared to term infants. METHODS: Between August and November 2006, all infants born in an academic and non-academic hospital with gestational age (GA) 25-42 weeks and without metabolical, congenital diseases or gastrointestinal disorders, were included. Infants were divided into four groups: (A) GA < or =30 weeks; (B) GA between 31 and 34 weeks; (C) GA between 35 and 36 weeks; (D) GA > or = 37 weeks (term born). RESULTS: A total of 198 infants (102 males); 32, 62, 33 and 71 infants in groups A, B, C and D, respectively, were included. With decreasing gestation a trend was found for delayed first PoM (p<0.001). Compared to term infants 79% (56/71), less preterm infants passed their first stool within 24 h after birth--group A: 44% (14/32); group B: 68% (42/62); and group C: 73% (24/33). With decreasing gestation a trend for prolonged PoM was found (p<0.001). The mean (SD) PoM duration was prolonged in group A: 7.8 days (2.5); group B: 4.3 days (2.4); and group C: 2.9 days (1.3) compared to term infants. Furthermore, PoM was associated with birth weights < or =2500 g (p = 0.03) and morphine therapy (p = 0.03). Duration of PoM was not associated with type of feeding, small for gestational age, large for gestational age or need for respiratory support. CONCLUSION: PoM was not only delayed but also prolonged in preterm infants. Duration of PoM was associated with GA, birth weight and morphine therapy.

A possible role of thymidine phosphorylase expression and 5-fluorouracil increased sensitivity in oropharyngeal cancer patients.

Thymidine Pi deoxyribosyltransferase (TP) is an enzyme involved in DNA synthesis up-regulated in tumours and it is also a pro-angiogenic factor. TP cannot activate capecitabine, because capecitabine first needs conversion by carboxylesterase and cytidine deaminase into 5-deoxy-fluorouridine. This compound can be activated by TP to 5-fluorouracil (5-FU). Although TP is not necessary for 5-FU toxicity, experimental data suggest that high levels of TP correlate with an enhanced response to 5-FU therapy. In this study, we have analysed by immunohistochemistry CD34, CD68 and TP positive cells in bioptic samples from 53 patients with T(1-3) N(0-1) M(0) oropharyngeal squamous cell carcinoma (OSC) and from 24 patients with non-dysplastic oropharyngeal leukoplakia (NDOLP). Results showed that the mean of TP-positive cells, CD68 positive macrophages and CD34 positive endothelial cells eval-uated as microvessel density (MVD) was significantly higher in OSC than in NDOLP. Moreover, at a median follow-up of 19 months, patients with TP expression and higher MVD showed a better survival rate as compared to those with low MVD, probably as a consequence of 5-FU-based therapy.We hypothesized a role for TP in oropharyngeal tumourigenesis and 5-FU activation in the adjuvant setting of OSC patients.

BG60S dissolution interferes with osteoblast calcium signals.

We investigated the influence of extracellular calcium concentration, caused by the dissolution of a bioactive glass with 60% of silicon (BG60S), on intracellular calcium (Ca(i) (2 +)) signals and expression of inositol 1, 4, 5-triphosphate receptors (InsP(3)R) in primary culture of osteoblasts. We found that BG60S caused an increase in Ca(i) (2 +) signals in this cell type. Additionally, osteoblasts pre-incubated in the presence of BG60S showed an increase in Ca(i) (2 +) when cells were stimulated with vasopressin. On the other hand, a decrease in Ca(i) (2 +) signals were observed in osteoblasts pre-treated with BG60S and stimulated with KCl. We furher found that in osteoblasts, the type I InsP(3)R is preferentially distributed in the nucleus while the type II InsP(3)R in the cytoplasm. Preincubation of osteoblasts with BG60S altered the receptor expression level, increasing the type I InsP(3)R in the nucleus and decreasing type II InsP(3)R in the cytosol. Together, our results showed that in osteoblasts, BG60S increased Ca(i) (2 +)signals and altered Ca(i) (2 +) machinery.

Biocompatibility evaluation of hydroxyapatite/collagen nanocomposites doped with Zn+2.

In this work, novel composites based on calcium phosphates (CaP)/collagen (COL) doped with Zn(+2) have been synthesized. They were characterized by SEM coupled to EDS microprobe in order to evaluate their morphology and chemical composition, respectively. The biocompatibility of these synthetic CaP/COL nanocomposites doped and undoped with Zn(+2) was investigated through osteoblast cell culture assay. Calcium phosphates were produced via aqueous precipitation routes where two different phases were obtained, hydroxyapatite (HAP) and biphasic hydroxyapatite-betatricalcium phosphate (HAPbetaTCP). In the sequence, the type-I collagen (COL) was added to the inorganic phase based on calcium phosphate and the mixture was blended until a homogenous composite was obtained. Zn(+2) aqueous solution (1.0 wt%) was used as the doping reagent. The cell viability and the alkaline phosphatase production of osteoblasts in the presence of the composites were evaluated and compared to control osteoblasts. Also, the biocompatibility of the composite was investigated through cell morphological analysis using optical microscopy of osteoblasts. All experiments were performed in triplicates (n = 3) from three different experiments. They were analyzed by variance test (ANOVA) and Bonferroni's post-test with differences statistically significant at p < 0.05. The results showed that the CaP/COL composites doped and undoped with Zn(+2) did not present alterations in cell morphology in 72 h and had similar cell viability and alkaline phosphatase activity to the control. All the tested CaP/COL composites showed adequate biological properties with the potential to be used in bone tissue replacement applications.

Hydrothermal growth of hydroxyapatite scaffolds from aragonitic cuttlefish bones.

Scaffolds of AB-type carbonated hydroxyapatite (HA) were successfully produced via hydrothermal transformation (HT) of aragonitic cuttlefish bones at 200 degrees C. The transformation was seemingly complete after 9 h of HT and no intermediate products were registered. Beyond low production cost, worldwide availability, and natural-biological origin of raw materials, the produced scaffolds preserved the initial structure of cuttlefish bone, featuring good biocompatibility in osteoblasts tests and ideal pore size ( approximately 80 microm in width and approximately 100 microm in height) and interconnectivity for supporting biological activities, such as bone tissue growth and vascularization. The highly channeled structure and the use of fresh cuttlefish bones favored the diffusion of the reaction solution towards the aragonite resulting in fast kinetics (after 1 h, hydroxyapatite was the dominant crystalline phase).

Citalopram serum and milk levels in mother and infant during lactation.

We present a case of intensified therapeutic drug monitoring (TDM) of citalopram in mother and newborn infant after clinically observed selective serotonin reuptake inhibitor (SSRI)-associated symptoms 2 weeks until 2 months after delivery. The SSRI-associated symptoms observed in the infant (up to 3 weeks after delivery) were irregular breathing, sleep disorders, hypotonia, and hypertonia. We conclude that the SSRI-associated symptoms in the infant represent citalopram withdrawal effects rather than side effects caused by breastfeeding. This case illustrates the importance of a flexible TDM program and a multidisciplinary approach in a hospital setting to deal with cases of drug-associated adverse effects, such as SSRI withdrawal effects.

The effect of a chitosan-gelatin matrix and dexamethasone on the behavior of rabbit mesenchymal stem cells.

Cartilage tissue has poor capability of self-repair, especially in the case of severe cartilage damage due to trauma or age-related degeneration. Cell-based tissue engineering using scaffolds has provided an option for the repair of defects in adult cartilage tissue. Mesenchymal stem cells (MSC) and chondrocytes are the two major cell sources for cartilage tissue engineering. The present study combined culture conditions of MSC in a chitosan-gelatin matrix in chondrogenic media to evaluate their effects on MSC viability and chondrogenesis for cartilage tissue engineering. MSC were harvested from rabbit bone marrows and cultured in chondrogenic media supplemented, or not, with dexamethasone in a chitosan-gelatin film (C-GF). The association of C-GF and dexamethasone promoted significant increase in cell adhesivity, viability and proliferation when compared to MCS cultured in media without dexamethasone or C-GF. In addition, dexamethasone promoted increase in the collagen concentration of MSC cultures. A reduction of alkaline phosphatase activity after three weeks of culture in chondrogenic media was verified. No influence of the C-GF or of dexamethasone was observed in this matter. Therefore, it is reasonable to suggest that biomaterial-based chitosan-gelatin and chondrogenic media supplemented with dexamethasone may stimulate the proliferation and differentiation of MSC according to the complex environmental conditions. The information presented here should be useful for the development of biomaterials to regulate the chondrogenesis of MSC suitable for cartilage tissue engineering.

Primary osteoblast cell response to sol-gel derived bioactive glass foams.

Bioactive glass macroporous structures were developed in this work to be used as scaffolds for bone tissue engineering applications. A sol-gel route was used to obtain glass foams with the introduction of a gas phase in the solution and by vigorous agitation of the sol-gel solution that contains a foam agent. Stable and homogeneous foams were formed near the gelation point, which were than dried and heat-treated. Macroporous structures with interconnected pores of up to 500 mu m, porosity as high as 88% and specific surface area of 92 m(2)/g were obtained. The porous glasses were tested in osteoblast cultures to evaluate adhesion, proliferation, collagen and alkaline phosphatase production. Osteoblast proliferation was higher in the presence of the foams as well as was the collagen secretion, when compared to control. The alkaline phosphatase production was not altered. Viable osteoblasts could be seen inside the foams, suggesting that the produced porous glass foams are a promising materials for bone repair, since it provides a good environment for the adhesion and proliferation of osteoblasts.

Scaffolds for bone restoration from cuttlefish.

Scaffolds of pure hydroxyapatite suitable for either direct clinical use or tissue-engineering applications were successfully produced via hydrothermal transformation of aragonite, obtained from fresh cuttlefish bones, at 200 degrees C followed by sintering. Beyond low production cost, worldwide availability and natural-biological origin of raw materials, the produced scaffolds have ideal pore size and interconnectivity features suitable for supporting biological activities, such as bone tissue growth and vascularization. Bioactivity in vitro tests were excellent: (a) rapid and pronounced formation of hydroxyapatite occurred when the scaffolds were immersed in simulated body fluid (SBF), and (b) outstanding proliferation of osteoblasts was registered. The produced scaffolds can be machined and shaped very easily at any stage of processing. Therefore, these ceramic scaffolds can satisfy both bioactivity demands and the requirements for shaping of tailor-made individualized implants, especially for randomly damaged bones.

Eating disorder variables and self image in Italian girls attending a weight control clinic.

OBJECTIVE: The aim of this study was to evaluate eating disorder variables and self image in Italian female adolescents asking for a weight control treatment. METHOD: Eating Disorder Inventory-2 (1991) and Offer Self-Image questionnaire (1989) were administered; 100 subjects (75 outpatients and 25 controls) were enrolled over a period of three months and divided into three study groups (normal, overweight and obese), and one control group. RESULTS: The relationship between BMI and problematic personality traits tends to be linear and positive. Obese adolescent females describe themselves in more negative terms than non-obese individuals and show a psychological profile similar to individuals with eating disorders, especially for Drive for Thinness and Interoceptive Awareness. Even in the absence of overt mental pathology, obesity can result associated to a psychological distress and it's a risk factor for mental health.

Thymidine phosphorylase profiles in nonmalignant and malignant pancreatic tissue. Potential therapeutic role of capecitabine on tumoral and endothelial cells and tumor-infiltrating macrophages.

The drug capecitabine (CAP) is a thymidine Pi-deoxyribosyltransferase (TP) activated oral fluorpyrimidine that generates 5-fluorouracil (5-FU), preferentially, within tumors. Here, in 38 patients with pancreatic cancer we analyzed immunohistochemical TP expression in pancreatic cancer tissue (PCT) and adjacent nonmalignant pancreatic tissue (ANMPT). In addition, a correlation with the main clinical pathological features was made. Furthermore, TP-positive macrophages (MO) isolated from neoplastic tissue were determined. The mean of TP-positive epithelial cells and endothelial cells in terms of microvessel density was significantly higher in PCT than in ANMPT. Because pancreatic cancer is sensitive to 5-FU, TP-activated oral CAP in tumoral and endothelial cells and tumor infiltrating MO could increase the concentration of 5-FU at tumor site, thus resulting in an enhanced antitumor activity.

[Diagnostic image (145). A girl with striae. Irreversible striae due to longterm use of corticosteroids]. / Diagnose in beeld (145). Een meisje met striae. Irreversibele striae ten gevolge van langdurig lokaal corticosteroïdgebruik.

A 9-year-old girl presented with irreversible striae, due to prolonged local corticosteroid use.