Institute for Maternal and Child Health

Trieste, Italy

Institute for Maternal and Child Health

Trieste, Italy
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Secchiero P.,University of Ferrara | Bosco R.,University of Ferrara | Celeghini C.,University of Trieste | Zauli G.,Institute for Maternal and Child Health
Current Pharmaceutical Design | Year: 2011

Nutlin-3 is a small molecule inhibitor of the MDM2/p53 interaction, which leads to the non-genotoxic p53 stabilization, activation of cell cycle arrest and apoptosis pathways. A series of recent studies have strengthened the concept that selective, non-genotoxic p53 activation by Nutlin-3 might represent an alternative to the current cytotoxic chemotherapy, in particular for pediatric tumors and for hematological malignancies, which retain a high percentage of p53 wild-type status at diagnosis. Like most other drugs employed in cancer therapy, it will be unlikely that Nutlin-3 will be used as a monotherapy. In this respect, Nutlin-3 shows a synergistic cytotoxic effect when used in combination with innovative drugs, such as TRAIL or bortozemib. Although Nutlin-3 is currently in phase I clinical trial for the treatment of retinoblastoma, its effects on normal tissues and cell types remain largely to be determined and will require further investigation in the future years. © 2011 Bentham Science Publishers Ltd.


Accardo A.P.,University of Trieste | Genna M.,University of Trieste | Borean M.,Institute for Maternal and Child Health
Human Movement Science | Year: 2013

Handwriting is the result of a process in which linguistic, psychomotor and biomechanical factors interact with physical maturation, cognitive development and learning. Digital tablets, which record the writing in real time, allow a kinematic analysis of written trace: the implemented algorithms analyze parameters as length, duration and speed of the components (trace between two pen-lifts) and strokes (trace between two minima of curvilinear velocity). The purpose of this work is to fill, at least for Italy, the lack of normative data on typical handwriting processes. This cross-sectional study will present data on 218 right-handed and Italian mother-tongue students, attending classes from 2nd to 8th grade. They performed specific tasks (tests of writing speed; transcription of a sentence accurately vs. speedily) by a digital tablet. The analysis showed many changes of the considered parameters across the classes, as in the horizontal, curvilinear mean and peak velocities of components and strokes, with higher values in the last years of schooling and a parallel decrease in the number of strokes/letter (improvement of automation). In conclusion, some of these parameters are useful for studying development and learning of writing and their values can be used as references to evaluate samples with different characteristics. © 2012 Elsevier B.V.


Gallotta V.,Catholic University of the Sacred Heart | Fanfani F.,Institute for Maternal and Child Health | Scambia G.,Catholic University of the Sacred Heart
Gynecologic Oncology | Year: 2014

Objective We report the technique to performminilaparoscopic nerve sparing radical hysterectomy (NSRH) in locally advanced cervical cancer. Methods Three patients aged 32, 53, and 51 respectively (median 46), with a median body mass index of 23 (18-26), one nulliparous and two pluriparous, were diagnosed with cervical squamous carcinoma on cervical biopsy, FIGO stage II B, and underwent a minilaparoscopic NSRH, bilateral salpingo-oophorectomy and systematic pelvic lymphadenectomy after neoadjuvant radiochemotherapy (pelvic irradiation in 22 fractions 1.8 Gy/day, totaling 39.6 Gy in combination with cisplatin 20 mg/m 2, 2-h intravenous infusion and 5-fluorouracil 1000 mg/m 2, 24-h continuous intravenous infusion, both on days 1-4 and 27-30) according to a protocol in our Institution [1,2]. Operative technique The procedures required a 5 mm 0 endoscope (Endoeye, Olympus Winter& Ibe GmbH, Hamburg-Germany) inserted in a trans-umbilical optical viewing port (Endopath Xcel, Ethicon Endo-surgery, Cincinnati, OH) and three additional sovrapubic 3-mm diameter ports placed. Three millimeter instruments were employed including atraumatic graspers, monopolar scissors, a suction-washing system (Karl Storz Endoskope-3 mm Instrument set, Tuttlingen Germany) and bipolar coagulator (Robi, Karl Storz). As already described, after pelvic and abdominal exploration, the operation starts with the coagulation and transection of the round ligament next to the pelvic wall and the opening of the anterior and posterior peritoneal layers of the broad ligament in order to enter the pelvic retroperitoneum. Once developed the paravesical and pararectal spaces the ureter can be easily identified. The uterine artery is then isolated and coagulated at its origin from umbilical artery. Before starting the pelvic lymphadenectomy, the dissection of the paravesical space laterally to the obliterated umbilical artery needs to be completed until the obturator nerve is identified. External and common iliac lymph nodes are removed from vessel surfaces by blunt or sharp dissection. Moreover, the obturator fossa is entered laterally and the obturator nerve and vessels are skeletonized before removing superficial and deep obturator lymph nodes. The anatomical margins for the pelvic lymph node dissection are medially the ureter, laterally the psoas muscle and the genitofemoral nerve, posteriorly the obturator nerve and cranially the mid portion of the common iliac artery. The same procedure was performed on the controlateral side. Once the ureter is identified, the infundibulopelvic ligament can be coagulated and transected. The pararectal space is then developed in a medial portion (Okabayashi space) and in a lateral portion (Latzko space), having the ureter in the middle. This maneuver allows the surgeon to identify the inferior hypogastric nerve, that appears approximately 2-3 cm dorsally of the ureter in the lateral part of the uterosacral ligament when entering the lateral parametrium. After its identification, this nerve is followed until it runs dorsally to the deep uterine vein. At this point the pelvic splanchnic nerves running from the S2-S4 roots of the sacral plexus join in the inferior hypogastric plexus with the inferior hypogastric nerves. After the identification of the above mentioned nerve structures, we performed a radical resection of the uterosacral and paracervical tissues according to the nerve sparing technique [3,4]. The paracervical tissue and the uterosacral ligaments were transected combining monopolar and bipolar devices with the vessel by vessel technique. Dissection of the ureteral tunnel and vesicovaginal spaces was accomplished with monopolar and blunt technique and with the aid of bipolar coagulation. At that point, the vaginal wall was identified and transected with a monopolar hook using pure section energy to avoid postoperative ureteral and bladder complications. The specimens were removed vaginally. The vaginal cuff was then closed transvaginally. A hydropneumatic test for bladder integrity was performed at the end of the procedure. The laparoscopic access points were only closed by steri-strips. Results All surgical procedures were completed as planned. Median operative time was 192 min (173-217) and the estimated blood loss was less than 50 mL in all cases. No post-operative complications occurred. Post-void residual was less than 100 mL in post-operative day 2. All patients were discharged on postoperative day 3. The pathology report revealed a median residual tumor of 8 mm (6-12) in all cervical specimens. The median width of parametrical tissue and length of vaginal cuff were 23 mm (20-27) and 18 mm (15-24), respectively. A median of 26 (21-33) lymph nodes had been harvested and were negative for metastasis. None of these three patients required adjuvant treatment. Over a median follow-up of 10 months all patients had no evidence of disease. Conclusions This surgical video testifies the technical feasibility ofminilaparoscopy NSRH producing surgico-pathologic data in line with what has recently been published [5,6].


Lazzerini M.,Institute for Maternal and Child Health
Evidence-Based Child Health | Year: 2013

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: De-Regil L, Suchdev PS, Vist GE, Walleser S, Pena-Rosas JP. Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age. Cochrane Database of Systematic Reviews 2011, Issue 9. Art. N.: CD008959. DOI: 10.1002/14651858.CD008959.pub2. © 2013 The Cochrane Collaboration.


Bernardi S.,University of Ferrara | Secchiero P.,University of Ferrara | Zauli G.,Institute for Maternal and Child Health
Recent Patents on Anti-Cancer Drug Discovery | Year: 2012

Multicellular organisms require apoptosis whereby the human body eliminates unnecessary and/or damaged cells. Apoptosis, or programmed cell death, can indeed be considered as a constitutive anti-cancer mechanism that seems to be defective in more than 50% of cancers. Molecular insights on the biology of the apoptotic process have led to the development of new anti-cancer strategies aiming at recovering and stimulating this process. Preclinical and clinical studies of our and other groups have demonstrated that targeting the extrinsic apoptotic pathway by various death receptors agonists is a safe and effective anti-cancer strategy, which thus may become a new cornerstone of cancer therapy. Here, we review the most recent acquisitions and patents on TRAIL or TRAIL mimetics, as well as the combination therapies that could be used with them. © 2012 Bentham Science Publishers.


Longo G.,Institute for Maternal and Child Health | Berti I.,Institute for Maternal and Child Health | Burks A.W.,North Carolina Childrens Hospital | Krauss B.,Boston Childrens Hospital | Barbi E.,Institute for Maternal and Child Health
The Lancet | Year: 2013

Food allergy is a serious health issue aff ecting roughly 4% of children, with a substantial eff ect on quality of life. Prognosis is good for the most frequent allergens with almost all children outgrowing their allergy. However, the long-term implications for disease burden are substantial for children with persistent allergies (eg, peanuts, tree nuts, fi sh, and shellfi sh) and for those with high concentrations of milk, egg, and wheat IgE. Antigen avoidance has been the time-honoured approach both for prevention and treatment. However, fi ndings from studies done in the past 5 years show that early contact with food can induce tolerance and desensitisation to foods. We review the epidemiology, natural history, and management of food allergy, and discuss the areas of controversy and future directions in research and clinical practice.


Becker G.E.,Institute for Maternal and Child Health | Remmington T.,Institute for Maternal and Child Health
The Cochrane database of systematic reviews | Year: 2014

BACKGROUND: Widespread recommendations from health organisations encourage exclusive breastfeeding for six months. However, the addition of other fluids or foods before six months is common in many countries and communities. This practice suggests perceived benefits of early supplementation or lack of awareness of the possible risks.OBJECTIVES: To assess the benefits and harms of supplementation for full-term healthy breastfed infants and to examine the timing and type of supplementation.SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (21 March 2014) and reference lists of all relevant retrieved papers.SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in infants under six months of age comparing exclusive breastfeeding versus breastfeeding with any additional food or fluids.DATA COLLECTION AND ANALYSIS: Two review authors independently selected the trials, extracted data and assessed risk of bias.MAIN RESULTS: We included eight trials (984 randomised infants/mothers). Six trials (n = 613 analysed) provided data on outcomes of interest to this review. The variation in outcome measures and time points made it difficult to pool results from trials. Data could only be combined in a meta-analysis for one secondary outcome (weight change). The trials that provided outcome data compared exclusively breastfed infants with breastfed infants who were allowed additional nutrients in the form of artificial milk, glucose, water or solid foods.In relation to the majority of the older trials, the description of study methods was inadequate to assess the risk of bias. The two more recent trials, were found to be at low risk of bias for selection and detection bias. The overall quality of the evidence for the main comparison was low.In one trial (170 infants) comparing exclusively breastfeeding infants with infants who were allowed additional glucose water, there was a significant difference favouring exclusive breastfeeding up to and including week 20 (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.05 to 1.99), with more infants in the exclusive breastfed group still exclusively breastfeeding. Conversely in one small trial (39 infants) comparing exclusive breastfed infants with non-exclusive breastfed infants who were provided with artificial milk, fewer infants in the exclusive breastfed group were exclusively breastfeeding at one week (RR 0.58, 95% CI 0.37 to 0.92) and at three months (RR 0.44, 95% CI 0.26 to 0.76) and there was no significant difference in the proportion of infants continuing any breastfeeding at three months between groups (RR 0.76, 95% CI 0.56 to 1.03).For infant morbidity (six trials), one newborn trial (170 infants) found a statistically, but not clinically, significant difference in temperature at 72 hours (mean difference (MD) 0.10 degrees, 95% CI 0.01 to 0.19), and that serum glucose levels were higher in glucose supplemented infants in the first 24 hours, though not at 48 hours (MD -0.24 mmol/L, 95% CI -0.51 to 0.03). Weight loss was also higher (grams) in infants at six, 12, 24 and 48 hours of life in the exclusively breastfed infants compared to those who received additional glucose water (MD 7.00 g, 95% CI 0.76 to 13.24; MD 11.50 g, 95% CI 1.71 to 21.29; MD 13.40 g, 95% CI 0.43 to 26.37; MD 32.50 g, 95% CI 12.91 to 52.09), but no difference between groups was observed at 72 hours of life. In another trial (47 infants analysed), we found no significant difference in weight loss between the exclusively breastfeeding group and the group allowed either water or glucose water on either day three or day five (MD 1.03%, 95% CI -0.18 to 2.24) and (MD 0.20%, 95% CI -1.18 to 1.58).Three trials with four- to six-month-old infants provided no evidence to support any benefit from the addition of complementary foods at four months versus exclusive breastfeeding to six months nor any risks related either morbidity or weight change (or both).None of the trials reported on the remaining primary outcomes, infant mortality or physiological jaundice.AUTHORS' CONCLUSIONS: We were unable to fully assess the benefits or harms of supplementation or to determine the impact from timing and type of supplementation. We found no evidence of benefit to newborn infants and possible negative effects on the duration of breastfeeding from the brief use of additional water or glucose water, and the quality of the evidence from a small pilot study on formula supplementation was insufficient to suggest a change in practice away from exclusive breastfeeding. For infants at four to six months, we found no evidence of benefit from additional foods nor any risks related to morbidity or weight change. Future studies should examine the longer-term effects on infants and mothers, though randomising infants to receive supplements without medical need may be problematic.We found no evidence for disagreement with the recommendation of international health associations that exclusive breastfeeding should be recommended for healthy infants for the first six months.


Objective To systemically review the evidence in support of World Health Organization guidelines recommending broad-spectrum antibiotics for children with severe acute malnutrition (SAM).Methods CENTRAL, MEDLINE, EMBASE, LILACS, POPLINE, CAB Abstracts and ongoing trials registers were searched. Experts were contacted. Conference proceedings and reference lists were manually searched. All study types, except single case reports, were included. Findings Two randomized controlled trials (RCTs), one before-and-after study and two retrospective reports on clinical efficacy and safety were retrieved, together with 18 pharmacokinetic studies. Trial quality was generally poor and results could not be pooled due to heterogeneity. Oral amoxicillin for 5 days was as effective as intramuscular ceftriaxone for 2 days (1 RCT). For uncomplicated SAM, amoxicillin showed no benefit over placebo (1 retrospective study). The introduction of a standardized regimen using ampicillin and gentamicin significantly reduced mortality in hospitalized children (odds ratio, OR: 4.0; 95% confidence interval, CI: 1.7-9.8; 1 before-and-after study). Oral chloramphenicol was as effective as trimethoprim-sulfamethoxazole in children with pneumonia (1 RCT). Pharmacokinetic data suggest that normal doses of penicillins, cotrimoxazole and gentamicin are safe in malnourished children, while the dose or frequency of chloramphenicol requires adjustment. Existing evidence is not strong enough to further clarify recommendations for antibiotic treatment in children with SAM. Conclusion Large RCTs are needed to define optimal antibiotic treatment in children with SAM with and without complications. Further research into gentamicin and chloramphenicol toxicity and into the pharmacokinetics of ceftriaxone and ciprofoxacin is also required.


Lazzerini M.,Institute for Maternal and Child Health
Bulletin of the World Health Organization | Year: 2011

To systemically review the evidence in support of World Health Organization guidelines recommending broad-spectrum antibiotics for children with severe acute malnutrition (SAM). CENTRAL, MEDLINE, EMBASE, LILACS, POPLINE, CAB Abstracts and ongoing trials registers were searched. Experts were contacted. Conference proceedings and reference lists were manually searched. All study types, except single case reports, were included. Two randomized controlled trials (RCTs), one before-and-after study and two retrospective reports on clinical efficacy and safety were retrieved, together with 18 pharmacokinetic studies. Trial quality was generally poor and results could not be pooled due to heterogeneity. Oral amoxicillin for 5 days was as effective as intramuscular ceftriaxone for 2 days (1 RCT). For uncomplicated SAM, amoxicillin showed no benefit over placebo (1 retrospective study). The introduction of a standardized regimen using ampicillin and gentamicin significantly reduced mortality in hospitalized children (odds ratio, OR:4.0; 95% confidence interval, CI: 1.7-9.8; 1 before-and-after study). Oral chloramphenicol was as effective as trimethoprim-sulfamethoxazole in children with pneumonia (1 RCT). Pharmacokinetic data suggest that normal doses of penicillins, cotrimoxazole and gentamicin are safe in malnourished children, while the dose or frequency of chloramphenicol requires adjustment. Existing evidence is not strong enough to further clarify recommendations for antibiotic treatment in children with SAM. Large RCTs are needed to define optimal antibiotic treatment in children with SAM with and without complications. Further research into gentamicin and chloramphenicol toxicity and into the pharmacokinetics of ceftriaxone and ciprofloxacin is also required.


Marzuillo P.,The Second University of Naples | Guarino S.,The Second University of Naples | Barbi E.,Institute for Maternal and Child Health
European Journal of Pediatrics | Year: 2014

Paracetamol (acetaminophen) is one of the most popular and widely used drugs for the treatment of pain and fever in children. This drug has multiple mechanisms of action, but its pharmacodynamic is still not well known. The central nervous system is the main site of action and it mirrors the paracetamol effect compartment. The recommended dosages and routes of administration should be different whether paracetamol is used for the treatment of pain or fever. For example, the rectal route, while being efficacious for the treatment of fever, should be avoided in pain management. Paracetamol is a safe drug, but some clinical conditions and concomitant drugs, which are frequent in clinical practice, may increase the risk of paracetamol toxicity. Therefore, it is important to optimize its administration to avoid overdoses and maximize its effect. The principal mediator of the paracetamol toxicity is the N-acetyl-p-benzo-quinone imine (NAPQI), a toxic product of the paracetamol metabolism, which could bind cysteine groups on proteins forming paracetamol-protein adduct in the liver. Conclusion: Although frequently prescribed, the concept of "effect compartment concentration" and the possible co-factors that could cause toxicity at recommended doses are not familiar to all pediatricians and general practitioners. We reviewed the literature concerning paracetamol mechanisms of action, we highlighted some relevant pharmacodynamic concepts for clinical practice, and we summarized the possible risk factors for toxicity at therapeutic dosages. © 2013 Springer-Verlag.

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