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Aim of our study is to verify the association between the genetic predisposition to hyperinsulinism due to the presence of the insulin gene (INS) I/I genotype and the development of sleep-related breathing disorders (SRBD) in obese children and adolescents. Two hundred and fifty-six obese children and adolescents (125 girls) have been investigated. As initial screening all subjects’ mothers filled out the Sleep Disturbances Scale for Children (SDSC). The Sleep-Disordered Breathing (SDB) scale has been taken into account. Successively, a subgroup of 34 patients belonging to the first (14 children) and the last (20 children) SDB score quintiles underwent an overnight polysomnography and the apnea-hypopnea index (AHI) was evaluated. All subjects were genotyped for the INS VNTRand fasting insulin levels were evaluated. The population was divided into two groups according to the genotype: the first group was comprehensive of patients homozygotes for class I allele and the second group was composed by class III allele heterozygotes and homozygotes patients. Subjects I/I showed statistically significant higher insulin levels (p<0.001) and SDB scores (p<0.001). Moreover, in the subgroup of patients investigated with polysomnography, class I homozygous subjects showed higher AHI compared to those patients carrying class III allele (p<0.001). Our data support the hypothesis that INS VNTRis associated with the development of SDB among obese children and adolescents.

One hundred consecutive patients with severe aplastic anemia (SAA) received horse antilymphocyte globulin (ALG), cyclosporin A (CyA), 6-methylprednisolone (6Mpred), and granulocyte colony-stimulating factor (G-CSF) as first-line therapy. The median age was 16 years (range, 1-72 years) and median neutrophil count was 0.2 × 109/L (range, 0-0.5 × 109/L). Trilineage hematologic recovery (at a median interval of 96 days from treatment) was seen in 77 patients (48 complete, 29 partial) after 1 (n = 50) or more courses of ALG (n = 27). Of the 23 nonresponders, 11 patients died at a median interval of 83 days (range, 16-1132 days), 6 were considered treatment failures and underwent transplantation, and 6 were pancytopenic. Cytogenetic abnormalities were seen in 11% of patients, clonal hematologic disease in 8%, and relapse of marrow aplasia in 9%. The actuarial survival at 5 years was 87% (median follow-up 1424 days): 76% versus 98% for patients with neutrophil counts less than versus greater than 0.2 × 109/L (P = .001) and 88% versus 87% for patients aged less than versus more than 16 years (P = .8). The actuarial probability of discontinuing CyA was 38%. Patients who did not achieve a white blood cell (WBC) count of 5 × 109/L during G-CSF treatment have a low probability of responding (37%) and a high mortality rate (42%). This update confirms a high probability for SAA patients of becoming transfusion independent and of surviving after treatment with ALG, CyA, 6Mpred, and G-CSF, with a significant effect of neutrophil counts on outcome. Problems still remain, such as absent or incomplete responses, clonal evolution, relapse of the original disease, and cyclosporine dependence. Early transplantation, also from alternative donors, may be warranted in patients with poor WBC response to G-CSF.

One hundred consecutive patients with severe aplastic anemia (SAA) received horse antilymphocyte globulin (ALG), cyclosporin A (CyA), 6-methylprednisolone (6Mpred), and granulocyte colony-stimulating factor (G-CSF) as first-line therapy. The median age was 16 years (range, 1-72 years) and median neutrophil count was 0.2 × 109/L (range, 0-0.5 × 109/L). Trilineage hematologic recovery (at a median interval of 96 days from treatment) was seen in 77 patients (48 complete, 29 partial) after 1 (n = 50) or more courses of ALG (n = 27). Of the 23 nonresponders, 11 patients died at a median interval of 83 days (range, 16-1132 days), 6 were considered treatment failures and underwent transplantation, and 6 were pancytopenic. Cytogenetic abnormalities were seen in 11% of patients, clonal hematologic disease in 8%, and relapse of marrow aplasia in 9%. The actuarial survival at 5 years was 87% (median follow-up 1424 days): 76% versus 98% for patients with neutrophil counts less than versus greater than 0.2 × 109/L (P= .001) and 88% versus 87% for patients aged less than versus more than 16 years (P= .8). The actuarial probability of discontinuing CyA was 38%. Patients who did not achieve a white blood cell (WBC) count of 5 × 109/L during G-CSF treatment have a low probability of responding (37%) and a high mortality rate (42%). This update confirms a high probability for SAA patients of becoming transfusion independent and of surviving after treatment with ALG, CyA, 6Mpred, and G-CSF, with a significant effect of neutrophil counts on outcome. Problems still remain, such as absent or incomplete responses, clonal evolution, relapse of the original disease, and cyclosporine dependence. Early transplantation, also from alternative donors, may be warranted in patients with poor WBC response to G-CSF.

The case for highly selective long range “proton assisted” electron transfer in biomolecules (PA-ET), involving the hopping of protons and hydrogen atoms along H-bond chains connecting two redox sites, is discussed and analyzed on systems closely resembling typical biochemical sequences. These systems consist of an electron acceptor, an H-bond/covalent-bridge chain and an electron donor, and monohydroparabenzoquinone as the electron acceptor and a xanthine-like molecule as the electron donor and acceptor species held together by one or more peptide bridges. It is shown that, in biochemical structures, despite the involvement of the imidol (oximine) form of the peptide link, (a) PA-ET is energetically efficient and (b) the rate constants for proton-transfer, which is arguably the rate-controlling step, are reasonably high, the transfer times being on the order of hundreds of picoseconds.

Desferrioxamine (DFO) has been suggested to improve erythropoiesis in end-stage renal failure independently of its aluminium (Al)-chelating effect. A possible synergistic effect of DFO and recombinant human erythropoietin (r-HuEpo) could be very useful in treating anaemia of chronic renal failure.

Patients with severe aplastic anemia (SAA) and a neutrophil (PMN) count of less than 0.5 x 10(9)/L are exposed to a high risk of early mortality when treated with antilymphocyte globulin (ALG) and steroids, with the major problem being infectious complications. The addition of human recombinant granulocyte colony-stimulating factor (rhG-CSF) to ALG may reduce early mortality by improving neutrophil counts in the short term. To test the feasibility of this approach, the SAA Working Party of the European Group for Blood and Marrow Transplantation (EBMT) designed a pilot study that included rhG-CSF (5 micrograms/kg/d, days 1 through 90), horse ALG (HALG; 15 mg/kg/d, days 1 through 5), methylprednisolone (2 mg/kg/d, days 1 through 5, then tapering the dose), and cyclosporin A (CyA; 5 mg/kg/d orally, days 1 through 180). Patients with newly diagnosed acquired SAA (untreated) and with neutrophil counts of < or = 0.5 x 10(9)/L were eligible. Forty consecutive patients entered this study and are evaluable with a minimum follow up of 120 days: the median age was 16 years (range, 2 to 72 years), the interval from diagnosis to treatment was 24 days, and the median PMN count was 0.19 x 10(9)/L. Twenty-one patients had hemorrhages, and 19 were infected at the time of treatment. Overall, treatment was well tolerated: the median maximum PMN count during rhG- CSF administration was 12 x 10(9)/L (range, 0.4 x 10(9)/L to 44 x 10(9)/L). There were three early deaths (8%) due to infection. Four patients (10%) showed no recovery, whereas 33 patients (82%) had trilineage hematologic reconstitution and became transfusion- independent at a median interval of 115 days from treatment. Median follow up for surviving patients is 428 days (range, 122 to 1,005). Actuarial survival is 92%: 86% and 100% for patients with PMN counts less than 0.2 x 10(9)/L or between 0.2 x 10(9)/L and 0.5 x 10(9)/L, respectively. This study suggests that the addition of rhG-CSF to ALG and CyA is well tolerated, is associated with a low risk of mortality, and offers a good chance of hematologic response. This protocol would appear to be an interesting alternative treatment for SAA patients with a low PMN count who lack an HLA-identical sibling.

The morphology of the delta and gamma forms of syndiotactic polystyrene (sPS) was investigated using scanning electron microscopy. The crystalline forms, delta and gamma, characterized by the chains in helical conformation, were obtained by solvent-induced crystallization from the amorphous glassy polymer. Dichloromethane and acetone were used to obtain the delta and the gamma form, respectively. The last form was obtained by thermal treatments of the delta form, too. The surface of the solvent-crystallized samples shows a texture characterized by oriented elements and cavities, whereas the internal part is microspherulitic in the case of the delta form and is more complex in the gamma form. At variance, the gamma form obtained by annealing the delta form shows a much more regular microspherulitic texture.

Summary Neutrophil granulocytes from 12 subjects with primary myeloperoxidase (MPO) deficiency (six totally deficient) and 16 patients with secondary partial MPO deficiency were tested using two different anti-MPO antibodies, in combination with either a flow-cytometric technique or an immunoalkaline phosphatase staining method. Results demonstrated three different cytofluorimetric patterns of immunoreactivity with the MPO protein: (a) a bright MPO antigenic expression, typical of patients with secondary MPO deficiency (comparable to that observed in the control group); (b) a medium MPO antigenic expression, typical of subjects with primary partial MPO deficiency; and (c) a dim MPO antigenic expression, characteristic of individuals with hereditary total MPO deficiency. No significant differences in granulocyte MPO reactivity were demonstrated for the two antibodies. Furthermore, in two individuals with complete primary enzyme deficiency, the single histogram analysis of MPO fluorescence determined by flow cytometry seemed to show that only 38% (case 1) and 44% (case 2) of neutrophils were reactive with the anti-MPO antibodies: the use of multiple histogram analysis in combination with Kolmogorov-Smirnov statistics allowed us to demonstrate that all the cells express a low density of MPO antigen. These data were more or less confirmed by the APAAP labeling method, which showed a reduced staining only in subjects with primary deficiency, while all patients with secondary deficiency had scores similar to those observed in controls (healthy subjects). Compared with the immunoenzymatic technique, the flow-cytometric procedure showed a higher sensitivity to MPO, being able to estimate even minor decreases in neutrophil MPO antigenic expression, as previously postulated by other authors. This work suggests that patients with primary MPO deficiency have different amounts of MPO antigens in the neutrophil granulocytes, and the levels of MPO fluorescence seem to decline concurrently with enzyme activity, thereby suggesting the presence of a diminished MPO production. In contrast, the normal antigenic reactivity of neutrophils from patients with acquired MPO deficiency indicates the presence of a functionally inactive form of the enzyme.

Patients with severe aplastic anemia (SAA) and a neutrophil (PMN) count of less than 0.5 × 109/L are exposed to a high risk of early mortality when treated with antilymphocyte globulin (ALG) and steroids, with the major problem being infectious complications. The addition of human recombinant granulocyte colony-stimulating factor (rhG-CSF) to ALG may reduce early mortality by improving neutrophil counts in the short term. To test the feasibility of this approach, the SAA Working Party of the European Group for Blood and Marrow Transplantation (EBMT) designed a pilot study that included rhG-CSF (5 μg/kg/d, days 1 through 90), horse ALG (HALG; 15 mg/kg/d, days 1 through 5), methylprednisolone (2 mg/kg/d, days 1 through 5, then tapering the dose), and cyclosporin A (CyA; 5 mg/kg/d orally, days 1 through 180). Patients with newly diagnosed acquired SAA (untreated) and with neutrophil counts of ≤0.5 × 109/L were eligible. Forty consecutive patients entered this study and are evaluable with a minimum follow up of 120 days: the median age was 16 years (range, 2 to 72 years), the interval from diagnosis to treatment was 24 days, and the median PMN count was 0.19 × 109/L. Twenty-one patients had hemorrhages, and 19 were infected at the time of treatment. Overall, treatment was well tolerated: the median maximum PMN count during rhG-CSF administration was 12 × 109/L (range, 0.4 × 109/L to 44 × 109/L). There were three early deaths (8%) due to infection. Four patients (10%) showed no recovery, whereas 33 patients (82%) had trilineage hematologic reconstitution and became transfusion-independent at a median interval of 115 days from treatment. Median follow up for surviving patients is 428 days (range, 122 to 1,005). Actuarial survival is 92%: 86% and 100% for patients with PMN counts less than 0.2 × 109/L or between 0.2 × 109/L and 0.5 × 109/L, respectively. This study suggests that the addition of rhG-CSF to ALG and CyA is well tolerated, is associated with a low risk of mortality, and offers a good chance of hematologic response. This protocol would appear to be an interesting alternative treatment for SAA patients with a low PMN count who lack an HLA-identical sibling.

In chronic renal failure, desferrioxamine (DFO) may improve erythropoiesis independent from its aluminium (Al) chelating effect. The mechanism of this action is still unknown.

The efficacy and toxicity of teicoplanin and vancomycin in the initial empirical antibiotic regimen in febrile, neutropenic patients with hematologic malignancies were compared in a prospective, randomized, unblinded, multicenter trial in the setting of 29 hematologic units in tertiary-care or university hospitals. A total of 635 consecutive febrile patients with hematologic malignancies and chemotherapy-induced neutropenia were randomly assigned to receive intravenously amikacin plus ceftazidime plus either teicoplanin at 6 mg/kg of body weight once daily or vancomycin at 1 g twice daily. An efficacy analysis was done for 527 evaluable patients: 275 treated with teicoplanin and 252 treated with vancomycin. Overall, successful outcomes were recorded for 78% of patients who received teicoplanin and 75% of those who were randomized to vancomycin (difference, 3%; 95% confidence interval [CI], -10 to 4%; P = 0.33). A total of 102 patients presented with primary, single-agent, gram-positive bacteremia. Coagulase-negative staphylococci accounted for 42%, Staphylococcus aureus accounted for 27%, and streptococci accounted for 21% of all gram-positive blood isolates. The overall responses to therapy of gram-positive bacteremias were 92 and 87% for teicoplanin and vancomycin, respectively (difference, 5%; CI, -17 to 6%; P = 0.22). Side effects, mainly represented by skin rash, occurred in 3.2 and 8% of teicoplanin- and vancomycin-treated patients, respectively (difference, -4.8%; CI, 0.7 to 8%; P = 0.03); the rate of nephrotoxicity was 1.4 and 0.8% for the teicoplanin and vancomycin groups, respectively (difference, 0.6%; CI, -2 to 1%; P = 0.68). Further infections were caused by gram-positive organisms in two patients (0.7%) treated with teicoplanin and one patient (0.4%) who received vancomycin (difference, 0.3%; CI, -0.9 to 1.0%; P = 0.53). Overall mortalities were 8.5 and 11% for teicoplanin- and vancomycin-treated patients, respectively (difference, -2.5%; CI, - 2 to 7%; P = 0.43); death was caused by primary gram-positive infections in three patients (1%) in each treatment group. When used for initial empirical antibiotic therapy in febrile, neutropenic patients, teicoplanin was at least as efficacious as vancomycin, but it was associated with fewer side effects.

Thirty contaminants of emerging concern (CECs) were identified and quantified in hospital wastewater (HWW) by LC-MS and their removal by solar photo Fenton (SPF) with ethylenediamine-N,N’-disuccinic acid (EDDS) at spontaneous pH (7.5) was compared to other solar driven advanced oxidation processes (AOPs) (namely, sunlight/persoxydisulphate (SPD) and sunlight/H2O2(SHP)). Almost all the detected CECs (28) are pharmaceuticals and belong to 13 different classes, with concentrations varied between 0.08µg/L (psychiatric drug) to 38.92µg/L (antidiabetic). First, the formation of iron-EDDS complexes was characterized by electrochemical methods to compare Fe2+and Fe3+behavior. The effect on a carbamazepine (CBZ) aqueous solution of solar driven Fe2+/EDDS and Fe3+/EDDS Fenton processes was comparatively evaluated to select the most effective one for advanced oxidation tests on real HWW and sunlight/Fe2+-EDDS/H2O2was the most effective one with 48% removal after 12.5kJ/L-1(78% total removal, 30% being under dark Fenton condition). SPF process was also more effective than SPD and SHP (60min sunlight exposure, 5kJ/L-1). Subsequently, the effect of the solar AOPs (SPF, Fe2+0.1mM, EDDS 0.2 Mm, H2O22.7 Mm; SPD, PD 1.48mM; SHP, H2O22.7 Mm; 60min sunlight exposure) was investigated in the treatment of the HWW and SPF resulted the most effective one, all CECs being removed from 70% to 100%.

To search for CDKL5gene mutations in boys presenting with severe early-onset encephalopathy and intractable epilepsy, a clinical picture very similar to that already described in girls with CDKL5mutations.