Management of paediatric Lyme disease in non-endemic and endemic areas: data from the Registry of the Italian Society for Pediatric Infectious Diseases.

The purpose of this investigation was to determine how specialists in paediatric infectious diseases (PIDs) manage children with suspected Lyme disease (LD) by comparing their approaches in Italian endemic and non-endemic areas. A cross-sectional survey of the PID specialists participating in the Italian Society for Pediatric Infectious Disease (SITIP) Registry of LD was carried out between 1 January and 30 April 2012. A total of 160 children (80 living in endemic areas and 80 living in non-endemic areas) were diagnosed as having LD between 1 January 2005 and 31 December 2011. The clinical manifestations were erythema migrans in 130 cases (81.3 %), arthritis in 24 (15.0 %) and neuroborreliosis in six (3.8 %). Significant differences from the recommendations concerning serology and the tests to undertake were mainly observed in the children with erythema migrans, especially those living in non-endemic areas (p < 0.05). The children with erythema migrans who lived in non-endemic areas were treated with antibiotics significantly less frequently than those living in endemic areas (p < 0.05), and significantly fewer children with erythema migrans or arthritis living in non-endemic areas were treated with amoxicillin in comparison with those living in endemic regions (p < 0.05). The duration of antimicrobial therapy was significantly shorter than recommended in the children with erythema migrans or arthritis, especially those living in non-endemic areas (p < 0.05). Paediatric LD is also present in areas of Italy in which it is not considered endemic, but knowledge concerning its management is generally poor among PID specialists and characterised by enormous gaps in non-endemic areas.

Abdominal asymmetry in a 17 year old girl.

The pseudopapillary pancreatic solid tumor (TPSP) is a rare malignancy typical of young adult women (only 12 pediatric cases from 2000 to 2009), it can recur and metastasize. The prognosis is usually good after radical surgical removal. We emphasize the importance of TPSP in differential diagnosis of retrogastric, peripancreatic masses especially in puberal females. We describe the case of an adolescent girl with an abdominal mass revealed as a rare pancreatic neoplasia.

Two novel POLG mutations causing hepatic mitochondrial DNA depletion with recurrent hypoketotic hypoglycaemia and fatal liver dysfunction.

BACKGROUND: Inherited mtDNA depletion syndromes (MDS) are a group of severe mitochondrial disorders resulting from defects in nucleus-encoded factors and often associated with severe or fatal liver failure. PATIENT: In this article, we describe the case of an 18-month-old patient with recurrent hypoketotic hypoglycaemia and fatal hepatic dysfunction with liver mtDNA depletion. METHODS: The assessment of mtDNA copy number was performed on leucocytes, liver and muscle biopsy by Quantitative Real Time PCR and total RNA from liver biopsy was used as a template to amplify the cDNA of the POLG1 gene. RESULTS: Sequence analysis identified two previously undescribed mutations (1868T>G and 2263A>G) located in the gene coding the catalytic subunit of mitochondrial DNA polymerase gamma (POLG), predicting an L623W and K755E amino acid change, respectively. Both mutations were located in the highly conserved linker region of the protein and were absent in more than 200 healthy unrelated control subjects. The identification of these two mutations allowed us to perform genetic counselling and prenatal diagnosis. CONCLUSION: Our data further expand the spectrum of POLG1 gene mutations and the unique phenotype reported (late onset isolated liver disease without lactic acidosis) increase the variability of clinical presentations associated with mutations in this gene.

[Short-stay observation in the Pediatric Emergency Room: a 2003-1993 comparison]. / L'osservazione temporanea in Pronto Soccorso pediatrico. Confronto 2003-1993.

AIM: To evaluate the effectiveness of Short-Stay Observation (SSO) in the paediatric Emergency Room (ER) according to changes over time of guidelines. METHODS: This retrospective study analyses the probability of discharge immediately from ER or after SSO and of hospital admission in Trieste during 2003 as compared with 1993. Subjects aged under 18 with respiratory, urinary tract, neurological and gastrointestinal pathologies, selected symptoms and injuries were studied. RESULTS: In 2003 the 86.2% of 6 350 patients enrolled in the study were discharged immediately, compared with the 81.7% of 5475 subjects in 1993 (RR 1.05, IC 95% 1.04-1.07), the 10.0% were discharged after SSO, compared with the 5.9% in 1993 (RR 1.71, IC 95% 1.50-1.95). The 3.8% of the subjects were admitted in 2003, compared to the 12.4% in 1993 (RR 0.30, IC 95% 0.26-0.35). The role of SSO was particularly significant in case of pneumonia, URI, urinary tract infections, seizures, gastroenteritis, abdominal pain, infant fever, injuries. CONCLUSIONS: The decrease of hospital admissions, pointed out in 2003, are related to a better choice of candidates for SSO and to changes in guidelines concerning the approach to urinary tract infections and seizures, the treatment of respiratory distress and gastroenteritis dehydration, and the early identification of predictors of injuries complications. The study confirms the effectiveness of SSO in both avoiding inappropriate admissions and reducing those with limited needs of hospital assistance, assuring the quality of care. The reduced hospital stay decreases child and his family discomfort and favours the care continuity due to the involvement of family paediatrician.

Aspartic protease inhibitors. An integrated approach for the design andsynthesis of diaminodiol-based peptidomimetics.

Aspartic proteases play key roles in a variety of pathologies, including acquired immunodeficiency syndrome. Peptidomimetic inhibitors can act as drugs to combat these pathologies. We have developed an integrated methodology for preparing human immunodeficiency virus (HIV)-1 aspartic protease diaminodiol inhibitors, based on a computational method that predicts the potential inhibitory activity of the designed structures in terms of calculated enzyme-inhibitor complexation energies. This is combined with a versatile synthetic strategy that couples a high degree of stereochemical control in the central diaminodiol module with complete flexibility in the choice of side chains in the core and in flanking residues. A series of 23 tetrameric, pentameric and hexameric inhibitors, with a wide range of calculated relative complexation energies (-47.2 to +117 kJ.mol-1) and predicted hydrophobicities (logPo/w = 1.8-8.4) was thus assembled from readily available amino acids and carboxylic acids. The IC50 values for these compounds ranged from 3.2 nM to 90 microM, allowing study of correlations between structure and activity, and individuation of factors other than calculated complexation energies that determine the inhibition potency. Multivariable regression analysis revealed the importance of side-chain bulkiness and rigidity at the P2, P2' positions, suggesting possible improvements for the prediction process used to select candidate structures.

Stereoselective synthesis of non symmetric dihydroxyethylene dipeptide isosteres via epoxy alcohols derived from alpha-amino acids.

(1R,2R,3S,4S)-4-Amino-3-hydroxy-1,2-epoxybutanes, accessible in four steps from L-aminoesters, react regio- and stereoselectively with diethyl aluminum cyanide to give (1R,2S,3S,4S)-4-amino-2,3-dihydroxynitriles. Hydrolysis yields hydroxylactones equivalent to 2,3-dihydroxy-4-aminoacids. The sequence provides a novel approach to dihydroxyethylene isosteres potentially useful for new HIV-protease inhibitors.