Folic acid, vitamin B12, and homocysteine levels during fasting and after methionine load in patients with Type 1 diabetes mellitus.

AIMS: To assess plasma concentrations of folic acid, vitamin B12, and total plasma homocysteine (tHCY) during fasting and after methionine load in young patients with Type 1 diabetes mellitus (T1DM). METHODS: We enrolled 41 young patients with T1DM without any sign of microvascular complications and 123 healthy controls in a 1:3 case-control study. Fasting and post-methionine load (PML) tHCY, folic acid, and vitamin B12 levels were measured in both groups. Data regarding chronological age, metabolic control (assessed by mean values of glycated hemoglobin in the last 12 months) and disease duration were also recorded. RESULTS: Fasting and PML tHCY levels were significantly lower in patients than in controls: 7.3+/-2.7 micromol/l vs 8.3+/-2.5 micromol/l (p=0.01), and 16.7+/-5.8 micromol/l vs 17.3+/-4.3 micromol/l (p=0.01), respectively. No correlation was found between fasting and PML tHCY levels and chronological age, disease duration, metabolic control, and insulin requirement. Patients had significantly higher vitamin B12 levels compared to controls: 767+/-318 pg/ml vs 628+/-236 pg/ml (p=0.003), while folic acid turned out to be lower in patients than in controls: 5.3+/-1.9 nmol/l vs 7.5+/-2.6 nmol/l (p<0.0001). CONCLUSIONS: Adolescents and young adults with T1DM without microvascular complications showed lower tHCY both during fasting and after methionine load. Lower folate concentrations in these patients might benefit from food fortification.

Volume targeted ventilation (volume guarantee) in the weaning phase of premature newborn infants.

OBJECTIVE: Several options are currently available in neonatal mechanical ventilation: complete breathing synchronization (patient triggered ventilation, synchronized intermittent positive pressure ventilation--SIPPV); positive pressure flow-cycled ventilation (pressure support ventilation, PSV); and volume targeted positive pressure ventilation (volume guarantee, VG). The software algorithm for the guarantee volume attempts to deliver a tidal volume (Vt) as close as possible to what has been selected by the clinician as the target volume. Main objectives of the present study were to compare patient-ventilator interactions and Vt variability in premature infants recovering from respiratory distress syndrome (RDS) who were weaned by various ventilator modes (SIMV/PSV + VG/SIPPV + VG and SIMV + VG). METHODS: This was a short-term crossover trial in which each infant served as his/her own control. Ten premature infants born before the 32nd week of gestation in the recovery phase of RDS were enrolled in the study. All recruited infants started ventilation with SIPPV and in the weaning phase were switched to synchronized intermittent mandatory ventilation (SIMV). Baseline data were collected during an initial 20-min period of monitoring with the infant receiving SIMV alone, then they were switched to SIPPV + VG for a 20-min period and then switched back to SIMV for 15 min. Next, they were switched to PSV + VG for the study period and switched back to SIMV for a further 15 min. Finally, they were switched to SIMV + VG and, at the end of monitoring, they were again switched back to SIMV alone. RESULTS: Each mode combined with VG discharged comparable Vts, which were very close to the target volume. Among the VG-combined modes, mean variability of Vt from preset Vt was significantly different. Variability from the target value was significantly lower in SIPPV and PSV modes than in SIMV (P < 0.0001 and P < 0.04 respectively). SIPPV + VG showed greater stability of Vt, fewer large breaths, lower respiratory rate, and allowed for lower peak inspiratory pressure than what was delivered by the ventilator during other modes. No significant changes in blood gases were observed after each of the study periods. CONCLUSIONS: With regards to the weaning phase, among combined modes, both of the ones in which every breath is supported (SIPPV/PSV) are likely to be the most effective in the delivery of stable Vt using a low working pressure, thus, at least in the short term, likely more gentle for the neonatal lung. In summary, we can suggest that the VG option, when combined with traditional, patient triggered ventilation, adheres very closely to the proposed theoretical algorithm, achieving highly effective ventilation.

Neonatal hearing screening model: an Italian regional experience.

OBJECTIVE: To produce a model for routine centralized hearing screening including all aspects of the screening, from diagnosis to psychological counseling and early rehabilitation. METHODS: A prospective observational study on a geographically defined pediatric population (Liguria region, northwestern Italy) and data collection in a data bank. The model proposed was created for the audiological screening of all newborns of the Liguria region. The model includes four phases: (1) preliminary identification of contractual, administrative, legal aspects; (2) screening for identification of congenital hearing impairment; (3) therapy and rehabilitation of identified subjects and genetic analysis; (4) epidemiology, data management, and workload management. To test the feasibility of the model proposed and to establish the workload required according to the resources available in the regional health plan, we performed a pilot study on all infants born in four of the 13 regional birth centers of Liguria region from 1 April 2001 to 30 September 2001. RESULTS: Out of the 3268 newborns enrolled during the 6-month pilot study, 3238 (99.1%) were screened with otoacoustic emissions (OAE), while screening was refused in 30 newborns (0.9%). OAE resulted in a 'pass' for 3180 newborns (98.2%) and a 'refer' in 58 (1.8%). The standard auditory brainstem response (ABR) test was performed in 156 newborns, 58 of them as a result of the 'refer' at the second OAE and 98 others at audiological risk. Results were positive or uncertain at first ABR in 45 patients. Workload was calculated on the basis of the data obtained in the pilot study to allocate financial and organizational resources. CONCLUSIONS: The results of the pilot study allowed project planning. We think that the screening model proposed is an example of how a regional organization can deliver improved quality care through a rationalization and optimization process.

Severe neurologic complications after hematopoietic stem cell transplantation in children.

OBJECTIVE: To describe and evaluate the incidence and risk factors of severe neurologic events (SNE) in pediatric recipients of allogeneic or autologous hematopoietic stem cell transplantation (HSCT) for hematologic or nonhematologic diseases. METHODS: Retrospective analysis of 272 consecutive children admitted to the G. Gaslini Children's Research Institute and given HSCT (70 from unrelated donors, 115 from related donors, and 87 autologous) between June 1985 and January 2001. RESULTS: Thirty-seven children (13.6%) developed SNE after a median of 90 days (range, 5 days to 8.8 years) after HSCT. Cyclosporine A (CSA) neurotoxicity was the most frequent SNE (n = 21), followed by irradiation or chemotherapy injury (n = 7), CNS infections (n = 7), cerebrovascular events (n = 3), and immune-mediated etiology SNE (n = 2). Eleven patients (30%) died because of the neurologic complications. Type of HSCT, treatment with total body irradiation (TBI), acute graft-vs-host disease (GvHD), GvHD >grade 2, and treatment with CSA were associated with a significant increased risk of SNE. CONCLUSIONS: Severe neurologic complications are frequent (14%) among children receiving HSCT, causing 8.5% of deaths after transplant. Transplant from allogeneic donor, especially if unrelated, the development of severe acute GvHD grade >2, and the use of TBI in the preparative regimen are the main risk factors for such complications.

A randomised control study comparing the Infant Flow Driver with nasal continuous positive airway pressure in preterm infants.

OBJECTIVE: To compare the effectiveness of the Infant Flow Driver (IFD) with single prong nasal continuous positive airway pressure (nCPAP) in preterm neonates affected by respiratory distress syndrome. DESIGN: Randomised controlled study. PATIENTS: Between September 1997 and March 1999, 36 preterm infants who were eligible for CPAP treatment were randomly selected for either nCPAP or IFD and studied prospectively for changes in oxygen requirement and/or respiratory rate. The requirement for mechanical ventilation, complications of treatment, and effects on mid-term outcome were also evaluated. RESULTS: Use of the IFD had a significantly beneficial effect on both oxygen requirement and respiratory rate (p < 0.0001) when compared with nCPAP. Moreover, O(2) requirement and respiratory rate were significantly decreased by four hours (p < 0.001 and p < 0.03 respectively). The probability of remaining supplementary oxygen free over the first 48 hours of treatment was significantly higher in patients treated with the IFD than with nCPAP (p < 0.02). IFD treated patients had a higher success (weaning) rate (94% v 72 %) and shorter duration of treatment (49.3 (31) v 56 (29.7) hours respectively; mean (SD)), although the difference was not significant. CONCLUSIONS: IFD appears to be a feasible device for managing respiratory distress syndrome in preterm infants, and benefits may be had with regard to oxygen requirement and respiratory rate when compared with nCPAP. The trend towards reduced requirement for mechanical ventilation, shorter clinical recovery time, and shorter duration of treatment requires further evaluation in a multicentre randomised clinical trial.

Comparison of patient hospitalization in chronic peritoneal dialysis and hemodialysis: a pediatric multicenter study.

Patient hospitalization was compared in 207 pediatric patients (age < or = 15 years at the start of dialysis) on chronic peritoneal dialysis (CPD) (127 patients) or center hemodialysis (HD) (80 patients), treated in 17 dialysis centers during the period 1989 to 1994, and followed up for at least three months. The hospitalization rate was expressed as hospital days per patient-month, and was calculated on the overall period of treatment and separately for the first and second year. Since the age at start of dialysis markedly differed between CPD (8.2 +/- 4.7 years) and HD (11.2 +/- 2.9 years) patients (with no HD patient younger than five years), results are separately presented in three patient groups: CPD patients aged < 5 years (A); CPD patients aged five to 15 years (B); HD patients (C). The duration of hospitalization was subdivided according to the following different causes: routine (monitoring of dialysis adequacy), complications of the modality, patient primary renal disease, and other causes. The results are presented in Table 1. A statistically significant difference in total days hospitalized was found between each of the two groups of CPD patients and the HD patients; the results for hospitalization for dialysis-related complications were higher in the group of younger children on CPD, while the difference between the two age-matched groups of patients on CPD and HD was not significant.

Safety of electronic molecular resonance adenoidectomy.

Adenoidectomy is one of the most frequent operations in children. In order to reduce hospital stay costs, today, this procedure is performed as day surgery. Even though adenoidectomy is not considered risky, some minor complications may occur, the most important being bleeding (0.5-8% incidence). The surgical technique used can influence considerably postoperative pain and time to recovery. This aspect is essential in the management of day surgery patients, for whom the need of safe and rapid maneuvers associated with early recovery determines the choice of the surgical procedure. Recently, we developed a surgical technique based on the use of an electronic molecular resonance tool associated with bendable suction electrocautery. This study was carried out on 600 patients, divided into two groups, the first undergoing ablation using the molecular resonance tool and the second undergoing curette adenoidectomy. The two groups were homogeneous for age, sex, surgical indications, and grade of adenoid hypertrophy. The following parameters were considered: duration of surgery, importance of intraoperative bleeding, time to cicatrization, incidence of bleeding complications. Duration of surgery and intra- and postoperative bleeding were much lower in the first group than in the group undergoing traditional adenoidectomy. In addition, rhinopharyngeal complete cicatrization, defined as absolute absence of pseudomembrane, was much quicker in the first group, as assessed by postoperative endoscopy. Another major advantage offered by the molecular resonance tool is the accuracy of surgery performed under visual control in a practically bloodless field. To sum up, this method, thanks to its technical features and safety, is particularly indicated in children and in patients with coagulation disorders.

Monothermal air caloric test in children.

We compared the efficacy of bithermal (BAT) and monothermal cold (MCAT) and warm (MWAT) air caloric tests in identifying labyrinthine function anomalies in the child. At first, we established confidence intervals of normality for both monothermal tests in 40 children (22 males, 18 females) aged 6-14 years, clinically healthy and normal as previously shown by BAT. Subsequently, we compared the results of BAT with those of MCAT and MWAT performed in 46 children (22 males, 24 females) aged 6-14 years, affected by multiple labyrinthine diseases. These results confirmed that, as in the adult, MCAT alone should not be used in the evaluation of labyrinthine function in vertiginous patients. As to MWAT, we obtained good sensitivity and specificity with respect to BAT (83% and 90% for 90% probability; 78% and 92.5% for 95% probability). Sensitivity values increased or decreased depending on the disease causing vertiginous symptoms, with decreased or increased number of false negatives. In our opinion, MWAT cannot replace BAT for the study of labyrinthine function in children. MWAT alone can be used when vertigo is ascribable to vestibular neuritis or to endogenous disease (dysmetabolic, dyscrasic, dysendocrine).

The air caloric test in children: subdivision and statistical analysis of the response.

Among a population of 200 children, suffering by dizziness that we examined in the ENT department of the G. Gaslini Institute of Genoa, we acquired and checked, through the statistical analysis, the data of an air caloric test (according to the standard stimulation method) performed in 20 children (resulted normal to neurological, ophtalmological and audiovestibuler examinations which included audiometry, tympanometry, spontaneous, positional and positioning nystagmus research, OKN and caloric tests) and subdivided into 10 s sequences. The statistical analysis of the results obtained showed the following: (1) in both cold and warm air caloric test, the response can be obtained already in the stimulation phase, requiring ENG recording to start at the beginning of stimulation; (2) even in children, response culmination occurs in a period ranging from 60 to 90 s from stimulation onset; therefore the Visual Suppression Test should be performed in this period to obtain more significant data; (3) in cold and warm test, considering SSCs, the response is constant and intense up to 130 and 110 s, respectively, from beginning of ENG recording. After these time ranges, the response is less intense and homogeneous, becoming poor and variable. In our opinion, this allows suspension of recording immediately after these periods without the risk of the excluding significant aspects of the response.

Polymorphisms in genes involved in folate metabolism as risk factors for NTDs.

Moderate hyperhomocysteinemia in pregnant women has been associated with an increased risk of neural tube defects (NTDs). Periconceptional supplementation with multi-vitamins containing folic acid may normalize homocysteine metabolism and decrease the NTD risk. The C677 T variant of the MTHFR gene coding for a thermolabile enzyme has been described as the first genetic risk factor that accounts for a group of NTDs characterized by low maternal folate status and high homocysteine concentrations. Another common mutation of the same MTHFR gene, A1298 C, has also been described as an NTD risk factor. In addition to abnormal folate metabolism, anything that compromises the internalization of folate into the cell may be involved in the pathogenesis of NTDs. For this reason, a common polymorphism in the RFC-1 gene encoding the reduced folate carrier protein (A80 G) could also be an additional NTD risk factor. In the present study we examined the genotypic distributions and the allele frequencies of MTHFR A1298 C and RFC-1 A80 G polymorphisms in DNA samples from healthy Italian individuals and compared them to the frequencies observed in NTD cases and their parents. By means of restriction enzymatic analysis, we determined that the frequency of the mutated C allele of the A1298 C mutation was 0.25 among control individuals, which is in the range of that recently reported in other ethnic groups. However, we report that the mutant C allele frequencies are significantly higher among NTD cases and case mothers than among controls (0.39, 0.44, 0.25). Furthermore, for the RFC-1 A80 G mutation, we found that the frequency of the G allele of the RFC-1 mutation was 0.46 in the control population, suggesting that this is a common polymorphism in the Italian population. In spite of the high prevalence of the 80 G/G genotype among healthy subjects, we observed an increased frequency of the G allele in NTD-affected children, and their mothers and fathers. These preliminary results indicate that both the MTHFR and RFC-1 polymorphisms may play a role in NTD risk, at least in the Italian population. Further studies should be directed toward the evaluation of the level of risk conferred by the mutant MTHFR and RFC-1 genotypes, as well as the interaction between these genetic determinants and other nutritional and environmental factors.

[Nosocomial infection caused by multiresistant Staphylococci in a neonatal and pediatric intensive care unit]. / Infezioni nosocomiali da stafilococchi multiresistenti in Terapia Intensiva neonatale e pediatrica.

We selected a paediatric population with a high risk of nosocomial infection formed by 116 newborns (42.8%) and 155 not newborns (57.2%) admitted into the ICU of the Giannina Gaslini Institute during the period 1-1-1992-30-9-1992; we compared it with a reference paediatric population studied in the same department during the period 1-1-1987-30-6-1988 formed by 310 newborns (44.3%) and 391 not newborns (55.7%). The purpose of this study is to evaluate the possible change in the incidence of colonizations and ICU specific nosocomial infections, the possible increase of nosocomial infections by multiresistant Staphylococci and the appearance of new multiresistant germs. The two populations obviously present similar factors of high risk of nosocomial infection (naso-tracheal intubation, mechanical ventilation, total parenteral nutrition, surgical procedures, thoracic and/or abdominal prothesis, etc.). The obtained data have been examined with the Chi-square method. The incidence of colonizations remained unchanged while we noted a significant increase (10.3% compared to 4.9%-p > 0.0014) of the "ICU" specific nosocomial infections; the increase regarded mainly the neonatal population (18.9% compared to 7%-p > 0.00001). Significant increase of the nosocomial infections by multiresistant Staphylococcus (Staphylococcus haemolyticus) with in vitro and in vivo resistance to teicoplanin. Furthermore, presence in the performed study of multiresistant gram negative germs.

Diagnosis and treatment of pediatric chronic osteomyelitis in developing countries: prospective study of 96 patients treated in Kenya.

The authors carried out a prospective study on 96 patients they treated in Kenya for chronic osteomyelitis from 2000 to 2009. All the patients received orthopedic surgery and antibiotic therapy, when possible based on the antibiotic sensitivity test. Among the 90 patients with at least 12 months' follow-up, 11 had osteomyelitis relapse (12.2%) and recovery rate was therefore 87.8% with no resulting disability. Risk factors for osteomyelitis relapse were investigated and previous treatment with beta-lactamines, predisposing to onset of methycillin-resistant Staphylococcus aureus (MRSA) infections (P = 0.03, OR = 5.74), and onset of osteomyelitis in the metaepiphyseal region (P < 0.0001) resulted statistically significant. Aim of the study was to evaluate the validity of our treatment of chronic osteomyelitis in Kenya on the basis of outcome.

Long-term results of catheter-based treatment of pulmonary atresia and intact ventricular septum.

OBJECTIVE: To review the outcome of patients with pulmonary atresia with intact ventricular septum after interventional perforation of the pulmonary valve, to assess the capability of this procedure to avoid neonatal or late intervention and to obtain a long-term biventricular repair. DESIGN: Retrospective interventional study and clinical follow-up study. SETTING: Tertiary referral centre. PATIENT POPULATION: Between November 1994 and December 2007, 40 neonates underwent radiofrequency perforation. Median age at pulmonary valvotomy was 28 hours (range 1-147 hours) and median weight was 2925 g (range 1900-4400 g). MAIN OUTCOME MEASURES: Procedural success and complication rates; early-term and long-term follow-up results. RESULTS: The procedure was successful in 39 patients but 16 of them needed neonatal surgery. The overall mortality was 7.5%. At a median follow-up of 82 months, four patients underwent a bidirectional Glenn procedure, whereas all the other patients achieved a biventricular circulation without any further intervention in 19 of them. Patients who died or needed additional intervention with or without biventricular circulation failure had a higher incidence of bipartite right ventricular (65% vs 15.8% of those not needing additional intervention; p = 0.004) and a lower median tricuspid Z value (-2 (range -3.5 to 1) vs -0.5 (range -2 to 1); p = 0.004)). CONCLUSIONS: The results confirm that percutaneous interventional perforation is an effective first-stage procedure in patients with pulmonary atresia with intact ventricular septum. The right heart appeared to be adequate to maintain a long-term biventricular circulation in the large majority of cases.

Breastfeeding in Northern Italy.

AIM: To describe the duration and type, as classified by World Health Organization (WHO) criteria, of breastfeeding in Ligurian newborns up to 1 year of age, and to identify possible related factors. METHODS: A prospective, observational study on a cohort of 757 women recruited in 10 hospitals in Northern Italy. Women were followed up by means of a questionnaire at discharge and by telephone interviews in the 4th, 12th, 24th and 48th weeks postpartum using the 'recall period' method. RESULTS: At discharge, 97.3% of mothers had started breastfeeding; regional breastfeeding rates at the 4th, 12th, 24th and 48th weeks were respectively 84.4%, 71.2%, 54.4% and 26.3%. Socio-demographic factors did not significantly influence these percentages. Median duration of breastfeeding was 6.5 months. No statistically significant differences were observed in duration of breastfeeding between women who started exclusive breastfeeding (EBF) and those who did predominant breastfeeding (PBF), while the difference was statistically significant when comparing complementary breastfeeding (CBF) with EBF and with PBF. CONCLUSIONS: Our study is the first regional experience in the Liguria region and represents a starting point for the diffusion of the culture of breastfeeding. Our results are satisfactory with regards to the overall duration of breastfeeding until the first year of life (26.3%), while duration of EBF (9.5% at the 24th week) is still unsatisfactory according to WHO objectives that include EBF for all children up to the sixth month of life.

Ligurian experience on neonatal hearing screening: clinical and epidemiological aspects.

AIM: Early identification and rehabilitation of newborns with congenital hearing impairment (HI) by Universal Neonatal Hearing Screening (UNHS). METHODS: The neonatal population was divided into two groups: babies with No Audiological Risk (NAR), and babies With Audiological Risk (WAR). NAR neonates underwent OAE testing, and in case of a doubtful (Refer) result, ABR testing was carried out. All WAR newborns underwent ABR testing within the third month of life. RESULTS: Between February 1, 2002 and December 31, 2004, UNHS was carried out on 32 502 newborns at the 13 regional birth centres, representing 98.7% of the whole regional neonatal population. The prevalence of HI in the population we tested was estimated at about 1 per thousand, while Bilateral Hearing Impairment (BHI) was estimated at 0.65 per thousand. A 3.7% prevalence of HI and a 2.8% prevalence of BHI was observed among the WAR population. Median age at the end of the diagnostic procedures was 6.7 months in the WAR population and 6.9 months in the NAR population. CONCLUSIONS: Our project is based on two levels of testing, which resulted in a 0.28% false-positive rate with 100% sensitivity and 99% specificity. Our screening is the first Italian experience that has been extended to a whole region and the results prove that regional neonatal hearing screening is feasible.