Diagnostic Approach to Acute Liver Failure in Children: A Position Paper by the SIGENP Liver Disease Working Group.

Acute liver failure (ALF) is a clinical condition characterized by the abrupt onset of coagulopathy and biochemical evidence of hepatocellular injury, leading to rapid deterioration of liver cell function. In children, ALF has been characterized by raised transaminases, coagulopathy, and no known evidence of pre-existing chronic liver disease; unlike in adults, the presence of hepatic encephalopathy is not required to establish the diagnosis. Although rare, ALF has a high mortality rate without liver transplantation (LT). Etiology of ALF varies with age and geographical location, although it may remain indeterminate in a significant proportion of cases. However, identifying its etiology is crucial to undertake disease-specific management and evaluate indication to LT. In this position statement, the Liver Disease Working Group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) reviewed the most relevant studies on pediatric ALF to provide recommendations on etiology, clinical features and diagnostic work-up of neonates, infants and children presenting with ALF. Recommendations on medical management and transplant candidacy will be discussed in a following consensus conference.

Autism and esophageal achalasia in childhood: a possible correlation? Report on three cases.

Chronic gastrointestinal symptoms are commonly reported in autistic patients. Dysphagia is often present, and it is generally related to behavioral eating disorders. The association between autism and esophageal achalasia has not been described in literature yet. We report our experience with three cases of autistic children we recently treated for esophageal achalasia. In the first case (a 14-year-old male), achalasia was diagnosed with barium swallow and esophageal manometry and was successfully treated with three pneumatic endoscopic dilatations (follow-up: 3 years). In the second case (a 12-year-old female), achalasia was diagnosed with barium swallow and esophageal manometry and was treated with Heller myotomy after two unsuccessful pneumatic endoscopic attempts (follow-up: 3 months). In the last case, a 15-year-old male underwent barium swallow and endoscopy that confirmed achalasia. He was treated with Heller myotomy, and he is asymptomatic at a 6-month follow-up. To our knowledge, this is the first report of a possible association between autism and esophageal achalasia. Because of the rarity of both diseases, their association in the same patient is unlikely to be casual even if speculation on their common etiology is impossible at present. This finding needs further confirmation, but it is sufficient, in our opinion, to indicate proper evaluation with barium swallow and/or manometry in any autistic children with eating difficulty.

Intestinal ischemia-reperfusion injury causes activation of bone marrow-derived progenitor cells.

INTRODUCTION: Bone marrow-derived circulating granulocyte and macrophage progenitor cells can contribute to the regeneration of ischemic tissue. Mobilization after heart or brain ischemia is well established, but it is unclear if this occurs after intestinal ischemia-reperfusion injury. Our aim was to evaluate bone marrow granulocyte-macrophage proliferation and the possible beneficial effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) in a model of intestinal ischemia-reperfusion. MATERIAL AND METHODS: After animal committee approval, anesthetized adult rats were divided into groups (n=4 per group) as follows: (i) control [C], (ii) 60 min intestinal ischemia [I], (iii) 60 min intestinal ischemia+360 min reperfusion [IR], (iv) 420 min sham operation [SH]. At sacrifice, bone marrow was removed, erythrocytes lysed and 1 50 000 nucleated cells plated in triplicate in 35 mm Petri dishes containing methylcellulose (MethoCult). After 11 days, granulocyte-macrophage colony-forming units (CFU-GM) were counted. In addition, to determine whether rhG-CSF injection stimulates progenitor cell activation, two further groups were studied: (v) 60 min intestinal ischemia+360 min reperfusion with injection of 50 microg/kg rhG-CSF at reperfusion [IR-G]; (vi) 420 min sham with rhG-CSF injected at 60 min [SH-G]. Data are expressed as median, range and IQR and compared using one-way ANOVA with Tukey's post-hoc test. RESULTS: Neither sham operation nor ischemia alone influenced the activation of bone marrow. However, IR caused a significant increase in bone marrow activation compared to control animals (p<0.01), ischemic animals (p<0.01) and sham operated animals (p<0.05). Administered at a dose of 50 microg/kg, which is commonly used in animal studies, rhG-CSF had no effect on bone marrow activation, and did not augment the effects of ischemia-reperfusion. At a higher dose (100 microg/kg), however, rhG-CSF resulted in the mortality of IR animals. CONCLUSIONS: Intestinal ischemia-reperfusion injury causes proliferation of bone marrow granulocyte-macrophage progenitors which contribute to long-term repair. This phenomenon is not augmented by the administration of exogenous rhG-CSF.

Assessment of a neonatal rat model of necrotizing enterocolitis.

INTRODUCTION: A neonatal rat model of necrotizing enterocolitis (NEC) is useful to investigate this devastating and obscure disease. The aim of this study was to assess a neonatal rat model of NEC to evaluate whether the histological appearance of the damaged intestine could be predicted by the clinical behaviour of the animals and the macroscopic appearance of the gut. MATERIALS AND METHODS: Neonatal rats were delivered at term and assigned either to a control group consisting of breastfeeding and no stress factors, or to a NEC group in which NEC was induced by gavage feeding + hypoxia + oral lipopolysaccharide (4 mg/kg/day once daily for the first 2 days of life). Clinical status was assessed on day 4 using a clinical sickness score (general appearance, response to touch, natural activity, body colour; 0 - 3 for each variable). Neonatal rats were sacrificed at 4 different time points: day 1, day 2, day 3, and day 4. At sacrifice, a macroscopic assessment of the gut was performed using a new scoring system based on: colour (0 - 2), consistency (0 - 2) and degree of dilatation (0 - 2). The resected gut was stained with haematoxylin/eosin, and evaluated microscopically by 2 independent blinded scorers, including a consultant histopathologist. The histology results were used to validate the macroscopic gut assessment. Results were compared by ANOVA and linear regression analysis. Ethics Committee and Home Office approvals were obtained. RESULTS: In the control group NEC was not present either macroscopically or histologically. The clinical sickness score was higher in the NEC group (median = 4.5; range = 2 - 6) compared to controls (median = 0; range = 0 - 1; p < 0.0001). In the NEC group the macroscopic appearance (from day 2) and histological score (from day 1) increased significantly (p < 0.0001) and were strongly correlated (r (2) = 0.74, p < 0.0001). CONCLUSIONS: The clinical behaviour and macroscopic appearance of the intestine are valid tools to assess gut damage in our neonatal rat model of NEC. This allows future studies that are not exclusively based on histology.

GH-releasing activity of Hexarelin, a new growth hormone releasing peptide, in infant and adult rats.

In recent years several synthetic peptides have been shown to be active in inducing GH secretion in different mammalian species. Among them GHRP-6, GHRP-1 and GHRP-2 have demonstrated high effectiveness and high selectivity in stimulating GH release. In the present paper we report studies on the GH-secreting properties of a GHRP analog in which Trp was substituted with the chemically more stable 2-Methyl-Trp. In studies performed in conscious 10-day old rats, the hexapeptide Hexarelin (His-D-2Me-Trp-Ala-Trp-D-Phe-Lys-NH2) resulted very active in stimulating GH secretion. In anesthetized adult male rats, i.v. administration of GHRP-6 or Hexarelin elicited prompt GH release with peak GH levels occurring within 10 min At all the doses tested, the 2 peptides possessed similar effectiveness in stimulating GH release. Hexarelin given s.c. elicited a long-lasting GH release and was slightly more effective than GHRP-6. In conclusion, these findings indicate that Hexarelin is a highly effective GH releaser and might represent a valuable diagnostic and/or therapeutic tool in clinical practice.

[Transposition of upper permanent canine and premolar. Orthodontic, surgical and conservative solutions]. / Trasposizione del canino e del premolare permanenti superiori: soluzioni ortodontiche, chirurgiche, conservative.

According to the bibliography and their personal experiences, the Authors take into account the transposition of the canine and first premolar, in order to discuss their causes and consider the different therapeutical possibilities. Three clinical cases are here treated.