Idiopathic neutropenia of infancy: Data from the Italian Neutropenia Registry

Autoimmune neutropenia of infancy (AIN) is characterized by low risk of severe infection, tendency to spontaneously resolve and typically onset at ≤4–5 years of age; it is due to auto-antibodies whose detection is often difficult. In case of negativity of 4 antineutrophils autoantibody tests, after having excluded ethnic, postinfection, drug induced, or congenital neutropenia, according to the Italian guidelines the patients will be defined as affected by “idiopathic neutropenia” (IN). We describe the characteristics of 85 IN patients enrolled in the Italian neutropenia registry: they were compared with 336 children affected by AIN. The 2 groups were clinically very similar and the main differences were detection age (later in IN), length of disease (longer in IN) and, among recovered patients, age of spontaneous recovery: the median age at resolution was 2.13 years in AINs and 3.03 years in INs (P = .00002). At bivariate analysis among AIN patients earlier detection age (P = .00013), male sex (P = .000748), absence of leucopenia (P = .0045), and absence of monocytosis (P = .0419) were significantly associated with earlier recovery; in the IN group only detection age (P = .013) and absence of monocytosis (P = .0333) were significant. At multivariate analysis detection age and absence of monocytosis were independently significant (P = 6.7e-05 and 4.4e-03, respectively) in the AIN group, whereas in the IN group only detection age stayed significant (P = .013).     

Plasmonic colloidal pastes for surface-enhanced Raman spectroscopy (SERS) of historical felt-tip pens

Surface-enhanced Raman spectroscopy (SERS) has been identified as a suitable technique for the analysis of colorants in works of art. Herein, the application of SERS to the identification of dye compositions in historical felt-tip pens is reported, which is of paramount importance for the development of appropriate conservation protocols for historical drawings. In this study, three pens (pink, green, and blue colors) belonging to the film director Federico Fellini were analyzed. SERS measurements were performed directly on the pen lines drawn on a commercial paper by the deposition of Ag colloidal pastes, which allowed fast in situ dye identification without the need for extraction or hydrolysis treatments. Eosin Y was identified as the only dye present in the pink pen ink, whereas erioglaucine was found to be the main dye component in green and blue pen inks. SERS also resulted in highly efficient identification of the individual dyes erioglaucine, crystal violet, and rhodamine present as a mixture in the blue pen ink. The high SERS sensitivity was ascribed to the plasmonic effects and efficient quenching of the fluorescence interference of dyes. A comparison with contemporary pen inks highlighted minor differences in the chemical composition. These results prove that SERS can be used as a fast and sensitive analytical tool for ink analysis that provides invaluable support for the general assessment of the date, provenance, and originality of the historical drawings as well as for the development of preventive conservation protocols.

SERS analysis performed with silver nanopastes allowed in situ identification of dye compositions of the historical felt-tip pens used by Federico Fellini.     

Inflammatory myoglandular polyp of the cecum: case report and review of literature

Background  

Inflammatory myoglandular polyp (IMGP) is a rare non-neoplastic polyp of the large bowel, commonly with a distal localization (rectosigmoid), obscure in its pathogenesis. Up till now, 60 cases of IMGP have been described in the literature, but none located in the cecum.     

Description of two measles outbreaks in the Lazio Region,Italy (2006-2007). Importance of pockets of low vaccine coverage in sustaining the infection

Background  

Despite the launch of the national plan for measles elimination, in Italy, immunization coverage remains suboptimal and outbreaks continue to occur. Two measles outbreaks, occurred in Lazio region during 2006-2007, were investigated to identify sources of infection, transmission routes, and assess operational implications for elimination of the disease.     

Sirolimus Therapy to Halt the Progression of ADPKD

Activation of mammalian target of rapamycin (mTOR) pathways may contribute to uncontrolled cell proliferation and secondary cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD). To assess the effects of mTOR inhibition on disease progression, we performed a randomized, crossover study (The SIRENA Study) comparing a 6-month treatment with sirolimus or conventional therapy alone on the growth of kidney volume and its compartments in 21 patients with ADPKD and GFR ≥40 ml/min per 1.73 m². In 10 of the 15 patients who completed the study, aphthous stomatitis complicated sirolimus treatment but was effectively controlled by topical therapy. Compared with pretreatment, posttreatment mean total kidney volume increased less on sirolimus (46 ± 81 ml; P = 0.047) than on conventional therapy (70 ± 72 ml; P = 0.002), but we did not detect a difference between the two treatments (P = 0.45). Cyst volume was stable on sirolimus and increased by 55 ± 75 ml (P = 0.013) on conventional therapy, whereas parenchymal volume increased by 26 ± 30 ml (P = 0.005) on sirolimus and was stable on conventional therapy. Percentage changes in cyst and parenchyma volumes were significantly different between the two treatment periods. Sirolimus had no appreciable effects on intermediate volume and GFR. Albuminuria and proteinuria marginally but significantly increased during sirolimus treatment. In summary, sirolimus halted cyst growth and increased parenchymal volume in patients with ADPKD. Whether these effects translate into improved long-term outcomes requires further investigation.Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder with major renal manifestations, which occurs in 1 of 400 to 1000 individuals.¹ ADPKD is genetically heterogeneous. Mutations of the two genes PKD1 (85% of the cases) and PKD 2 (15% of cases), encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively, are implicated in the disease development.² The functions of PC1 and PC2 have not been defined with certainty; however, PC1 is thought to interact with and regulate PC2, which is a member of a subfamily of transient receptor potential channels³ and may act as a cation channel allowing Ca²⁺ entry from the extracellular environment. Consistent with the PC1/PC2 complex having a role in Ca²⁺ regulation, PKD epithelial cells display altered intracellular Ca²⁺ homeostasis,⁴ which alters the response to increased levels of intracellular cAMP.^5–7Another change consistently found in PKD cells is activation of the Ser/Thr kinase mammalian target of rapamycin (mTOR), an enzyme that coordinates cell growth, cell-cycle progression, and proliferation.⁸ mTOR is made up of two distinct complexes: mTORC1 and TORC2. The direct downstream targets of mTORC1, the eukaryotic initiation factor 4E-binding protein and ribosomal protein S6 kinase (p70S6K1),^9,10 tightly regulate the translational initiation machinery to control cell growth and proliferation.⁸ In vitro studies demonstrated that the N-terminal cytoplasmic domain of PC1 co-localizes and interacts with tuberin.¹¹ Activated phospho-mTOR and p70S6K are induced in cyst-lining epithelial cells in cysts from human and mouse kidneys.¹¹ Moreover, p70S6K is increased in Han:SPRD rat kidneys with PKD.¹² These observations led to the hypothesis that defects in PC1 in ADPKD promote disruption of the tuberin-mTOR complex, leading to aberrant mTOR activation and signaling.¹¹ There is also evidence that IGF-1 by binding to its receptor is a major regulator of the mTOR pathway via signaling to phosphatidylinositol-3 kinase, protein kinase B (Akt), and mTOR.⁸ Increase in IGF-1 mRNA levels in the kidneys of the pcy mouse model of PKD¹³ and in IGF-1 protein in Han:SPRD rats¹⁴ has been reported. In addition, the amount of phospho-Akt in cystic Pkd1^−/− mouse kidneys was more than that in wild-type kidneys.¹⁵ Thus, if mTOR is such a converging point in PKD cells, it would be worthwhile as a possible drug target for treatment of renal cystic disorders.Sirolimus (originally referred to as rapamycin) is a macrocyclic lactone that is derived from Streptomyces hygroscopicus and exerts antiproliferative and growth-inhibiting effects as well as antifibrotic effect by inhibition of the mTOR enzyme.^16,17 The drug has been used in kidney transplant recipients as part of maintenance immunosuppressive therapy¹⁸ and more recently as an antitumor agent^19,20 and in drug-eluting stents to prevent coronary artery stenosis.²¹ Short-term treatment with sirolimus markedly reduced kidney size and lowered renal total cyst volume (TCV) density in PKD animal models.^11,12,22 In addition, in renal transplant recipients who had progressed to ESRD because of ADPKD, the size of native kidney and liver cysts decreased while on mTOR inhibitor therapy but did not change appreciably during treatment with other immunosuppressants.^11,23Thus, to assess formally the risk/benefit profile of mTOR inhibitor therapy in PKD, we designed the Sirolimus Treatment in Patients with Autosomal Dominant Polycystic Kidney Disease: Renal Efficacy and Safety (SIRENA; http://clinicaltrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT00491517","term_id":"NCT00491517"}}NCT00491517), a proof-of-concept, randomized clinical trial aimed to compare the changes in total kidney volume (TKV) and in the kidney''s various compartments. This was assessed by serial computed tomography (CT) scan evaluations during 6 months of treatment with sirolimus or conventional therapy alone in 21 patients with ADPKD and normal or moderately decreased kidney function. The study secondarily evaluated whether and to which extent treatment-induced changes in kidney volume and structure translated into concomitant changes in GFR as assessed by standard techniques. The results of these analyses formed the basis of this report.