F. Zacchello | Università degli Studi di Padova (original) (raw)
Papers by F. Zacchello
Clinical chemistry, 1998
We describe a new HPLC method for the simultaneous determination of lactulose and mannitol in uri... more We describe a new HPLC method for the simultaneous determination of lactulose and mannitol in urine, in which cation-exchange chromatography and evaporative light-scattering detection are used. The two sugars are orally administered for the estimation of intestinal permeability in children. Samples were purified by solid phase extraction on a C18 cartridge and subsequent addition of anion-exchange resin. Cellobiose may be used as an internal standard. The chromatographic separation was carried out in 16 min at a flow rate of 0.5 mL/min, using deionized water as the mobile phase. Within-run precision (CV) measured at three concentrations was 1.6-2.3% for lactulose and 1.0-1.9% for mannitol. Between-run CVs were 2.1-4.1% and 1.3-2.7% for lactulose and mannitol, respectively. Analytical recovery of both sugar probes was 97-101%. The detection limits (signal-to-noise ratio = 3) were 0.82 mg/L for lactulose and 0.65 mg/L for mannitol. The lactulose/ mannitol ratio in control subjects was...
Pediatric Pulmonology, 1998
The measurement of exhaled nitric oxide concentrations [NO] may provide a simple, noninvasive mea... more The measurement of exhaled nitric oxide concentrations [NO] may provide a simple, noninvasive means for measuring airway inflammation. However, several measurement conditions may influence exhaled NO levels, and ambient NO may be one of these. We measured exhaled NO levels in 47 stable asthmatic children age 5 to 17 years and in 47 healthy children, gender and age matched. Exhaled [NO] in expired air was measured by a tidal breathing method with a chemiluminescence analyzer, sampling at the expiratory side of the mouthpiece. NO steady-state levels were recorded. In order to keep the soft palate closed and avoid nasal contamination, the breathing circuit had a restrictor providing an expiratory pressure of 3-4 cm H 2 O at the mouthpiece. To evaluate the effect of [NO] in ambient air, measurements were randomly performed by breathing ambient air or NO-free air from a closed circuit.
Pediatric Neurology, 2005
This report presents the long-term (36 months) neurologic outcome in 12 neonates and 9 children w... more This report presents the long-term (36 months) neurologic outcome in 12 neonates and 9 children who survived after extracorporeal membrane oxygenation and attempts to identify its prognostic indicators through a prospective study in the pediatric intensive care unit of a university hospital. Outcome assessment, neurodevelopmental tests, electroencephalogram, auditory evoked potentials, visual evoked potentials, and somatosensory evoked potentials, cerebral sonography, or cerebral tomography were evaluated at the end of bypass and at 6, 12, 24, and 36 months after extracorporeal membrane oxygenation. "Before extracorporeal membrane oxygenation" variables (oxygenation index, pH, oxygen arterial partial pressure) and "during extracorporeal membrane oxygenation" variables (pH, oxygen arterial partial pressure, duration of bypass, clotting activated time, electroencephalogram) were also analyzed. A negative neurologic outcome (Glasgow Outcome Score different from "good recovery" or neurodevelopmental score less than 70) 12 months after extracorporeal membrane oxygenation was documented in 8.3% of neonates and in 30% of children who survived. There was no further change in subsequent evaluations (24 and 36 months follow-up). The most abnormal electroencephalogram during extracorporeal membrane oxygenation, the first electroencephalogram, neuroimaging score, and somatosensory evoked potentials after extracorporeal membrane oxygenation treatment were associated with negative neurologic outcome. The study documented that neonates and children treated with extracorporeal membrane oxygenation require long-term follow-up; electroencephalogram, neuroimaging score, and somatosensory evoked potentials have prognostic value for abnormal neurologic outcome.
The Lancet, 1988
Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled... more Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled vocabulary for indexing life sciences content.< br/> Note that some records do not have MeSH. These include Patents and the latest PubMed and PubMed Central records.
Journal of Pediatric Gastroenterology and Nutrition, 1990
Unlike adults (greater than 60% of cases), it is rare to find the chronic hepatitis B virus (HBV)... more Unlike adults (greater than 60% of cases), it is rare to find the chronic hepatitis B virus (HBV) carrier status with normal transaminases among children. The aim of this study was to investigate whether this status would depend on the duration of HBV infection, that is, whether chronic hepatitis in childhood would lead to the asymptomatic carrier status in later life. We reexamined all of our patients with chronic HBV infection of greater than 10 years' duration and with histologically documented chronic hepatitis during childhood. This was a group of 36 adolescents and young adults. All subjects were screened for tumor using alpha-fetoprotein assay and hepatic ultrasound. Eight patients with cirrhosis underwent esophageal fiberoptic endoscopy. All patients were in good general condition, with no clinical signs of liver failure. Only two patients had abnormal transaminase levels, both of whom had evidence of delta infection. All but one patient became anti-HBe positive. Five cases had HBsAg clearance. (Seventy-one percent of patients were HBeAg positive and 14% anti-HBe positive at the onset of the disease.) Hepatic ultrasound revealed no tumors in any of the subjects, and fiberoptic endoscopy demonstrated no esophageal varices. This study suggests that (a) chronic hepatitis and asymptomatic carrier status may be subsequent stages of the B virus infection; and (b) chronic hepatitis in childhood is generally benign and may evolve into an asymptomatic carrier status. The main problem with the chronic carrier status is probably the increased risk of hepatocellular carcinoma.
Intensive Care Medicine, 1996
Introduction: Permissive hypercapnia (PH) is a beneficial strategy for patients with acute respir... more Introduction: Permissive hypercapnia (PH) is a beneficial strategy for patients with acute respiratory distress syndrome (ARDS) to minimize barotrauma by decreasing the peak inspiratory pressure (PIP). Hypercapnia and hypoxia cause pulmonary vasoconstriction, pulmonary artery (PA) hypertension, and, thus, an increased afterload to the right ventricle. This increased afterload may result in increased right ventricular (RV) work load and subsequent RV dysfunction. One therapeutic approach is the use of inhaled nitric oxide (iNO), a selective PA vasodilator. The objectives of this study were to test the hypothesis that in a swine model of ARDS with PH, iNO would improve RV work load and not change intrinsic RV contractility.
European Respiratory Journal, 1998
European Journal of Pediatrics, 1997
We followed the clinical course of 21 infants with bronchopulmonary dysplasia enrolled in a prosp... more We followed the clinical course of 21 infants with bronchopulmonary dysplasia enrolled in a prospective home O2 therapy programme during a 4-year-period. Mean gestational age was 28.5 weeks (range, 25-36 weeks) and mean birth weight 1093 g (range 630-2750 g). Infants were regularly monitored to maintain pulse oximeter O2 saturation over 94%-95%. The source of O2 was liquid oxygen and was delivered by nasal cannula. During the follow up oxygenation was assessed by SatO2 measurement, cardiac function by Doppler echocardiography and respiratory function by the occlusion technique. All patients had an ophthalmological follow up. The mean age of the infants at discharge was 3.7 months (range 1.7-8.6) and mean weight 2830 g (range 2150-3780 g). At discharge 8 infants had right ventricular hypertrophy (RVH) and four of them had pulmonary hypertension. Mean duration of home O2 therapy was 97 days (range 15-320 days) and the mean age of discontinuation of O2 was 6.9 months (range 3-14.7 months). The cardiological follow up was benign: the ECG signs of RVH disappeared by 12 months of age in six out of eight infants and the right ventricular pulmonary pressure, as measured by the Doppler method, normalised in the four patients in whom it was detected. No relationship was found between respiratory mechanics and the duration of O2 therapy. Weight gain was poor with mean growth at the 3rd percentile for females and just below the 3rd percentile for males. Twelve of the 21 infants required 25 rehospitalizations. No one presented deterioration of retinopathy of prematurity that was present in 16 infants at discharge; at 12 months retinopathy was resolved in 14 infants. A total of 2025 hospital days were saved, representing a significant financial saving. Home O2 therapy permits the safe early discharge of O2-dependent BPD infants and it reduces significantly the length of time spent in hospital which represents a considerable financial saving.
European Journal of Pediatrics, 1994
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common inherited disorder of mi... more Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common inherited disorder of mitochondrial fatty acid b-oxidation in humans. To better understand the pathogenesis of this disease, we developed a mouse model for MCAD deficiency (MCAD À/À ) by gene targeting in embryonic stem (ES) cells. The MCAD À/À mice developed an organic aciduria and fatty liver, and showed profound cold intolerance at 4 8C with prior fasting. The sporadic cardiac lesions seen in MCAD À/À mice have not been reported in human MCAD patients. There was significant neonatal mortality of MCAD À/À pups demonstrating similarities to patterns of clinical episodes and mortality in MCAD-deficient patients. The MCAD-deficient mouse reproduced important aspects of human MCAD deficiency and is a valuable model for further analysis of the roles of fatty acid oxidation and pathogenesis of human diseases involving fatty acid oxidation. Citation: Tolwani RJ, Hamm DA, Tian L, Sharer JD, Vockley J, et al. (2005) Medium-chain acyl-CoA dehydrogenase deficiency in gene-targeted mice. PLoS Genet 1(2): e23.
European Journal of Cancer, 1998
We conducted a mutation analysis of the most conserved region of the neurofibromatosis type 1 (NF... more We conducted a mutation analysis of the most conserved region of the neurofibromatosis type 1 (NF1) gene, the guanine triphosphatase (GTPase) activating protein (GAP)-related domain (NF1 GRD), to which the function of tumour suppressor is attributed. Sixty primary neuroectodermal tumours were analysed. The rationale for the study was based on the likelihood of finding structural alterations resulting in loss of function of this region in tumours of neuroepithelial tissues, where the activity of neurofibromin seems to be crucial in regulating the mechanisms of signal transduction and cell transformation mediated by p21 ras. Following analysis of the whole NF1 GRD sequence, no mutations were identified in the tumours analysed. We conclude that the loss of NF1 gene tumour suppressor function, that might lead or contribute to the development of malignancies in neuroectodermal tissues, is not due to structural abnormalities of the region of the gene which interacts with p21 ras.
A nonradioactive in situ hybridization technique was utilized for the rapid and early diagnosis o... more A nonradioactive in situ hybridization technique was utilized for the rapid and early diagnosis of cytomegalovirus (CMV) infection in children undergoing kidney transplantation. The cellular samples were obtained directly from the organs thought to be affected on the basis of clinical findings: bronchoalveolar lavage during interstitial pneumonia (7 samples from 6 cases); fine-needle aspiration biopsy (FNAB) of the liver during acute hepatitis (1 case); kidney FNAB and peripheral blood where there was a greater than or equal to 25% creatinine rise with or without fever (26 episodes). Standard virus isolation procedures and an immunofluorescent technique on short-term cultures of human fibroblast cells were performed as a control. 6/23 children followed had a symptomatic CMV infection (4 had interstitial pneumonia; 1 had acute hepatitis, and there was 1 case of creatinine rise with fever). In all cases, the diagnosis was provided by in situ hybridization in less than 24 h. These results were confirmed 48 h later by immunofluorescence and after 5-25 days by standard viral cultures. In situ hybridization with a biotinylated probe proved to be a rapid and sensitive method for diagnosis of CMV disease, when performed on specimens obtained from the involved organs at an early stage of the infection. This diagnostic approach allowed a specific antiviral therapy to be undertaken promptly.
American Journal of Respiratory and Critical Care Medicine, 1997
Recently, it has been demonstrated that paranasal sinuses are an important site of nitric oxide (... more Recently, it has been demonstrated that paranasal sinuses are an important site of nitric oxide (NO) production in the upper airways. The aim of this study was to evaluate the NO nasal concentration in children with acute maxillary sinusitis before and after treatment with antibiotic therapy. We performed NO nasal measurements in 16 children 4 to 13 yr of age with acute maxillary sinusitis and compared values with 16 age-and sex -matched healthy control subjects. The diagnosis of acute sinusitis was done by clinical signs and symptoms in addition to radiographic examination. NO nasal concentrations were measured by a chemiluminescence analyzer. Nasal NO steady state during oral breathing was recorded. The mean ± SEM NO nasal concentration in children with sinusitis was 70 8.7 parts per billion (ppb) and increased significantly to 220 ± 15 ppb (p < 0.001) after antibiotic therapy (amoxicillin/clavulanate). NO values after recovery from sinusitis were similar to those of healthy control subjects (245 ± 15 ppb, p = NS). NO nasal measurements were also performed before and after antibiotic treatment in nine children 4 to 12 yr of age with symptoms of upper respiratory tract infection but no symptoms of sinusitis. In these children NO nasal levels were 249 ± 32 ppb and did not change (p = NS) after antibiotic therapy. We conclude that during acute maxillary sinusitis the concentration of nasal NO is largely decreased, probably because of an impaired flow of NO from the paranasal sinuses, and that NO returns to normal levels after antibiotic therapy. Baraldi E, Azzolin NM, Biban P, Zacchello F. Effect of antibiotic therapy on nasal nitric oxide concentration In children with acute sinusitis AM J RESPIR CRIT CARE MED 1997;155:1680-1683.
American Journal of Respiratory and Critical Care Medicine, 2000
It is known that exhaled nitric oxide (ENO) is increased in asthmatic individuals, probably as an... more It is known that exhaled nitric oxide (ENO) is increased in asthmatic individuals, probably as an expression of airway inflammation, but no studies have been reported of ENO and exercise-induced bronchoconstriction (EIB). We assessed the effect of a treadmill exercise challenge on ENO concentration in 24 asthmatic children aged 11.2 +/- 0.4 yr (mean +/- SEM). According to the presence or absence of EIB, the children were divided into an EIB group (n = 10) and a non-EIB group (n = 14). ENO was measured with a single-breath reservoir technique. FEV(1), ENO, and heart rate were measured at baseline and 1, 6, 12, and 18 min after the end of exercise. We also measured ENO in 18 healthy control children aged 10.8 +/- 0.6 yr, of whom nine underwent an exercise challenge identical to that of the asthmatic children. After the exercise test, the mean decrease in FEV(1) was 34% in the EIB group and 5% in the non-EIB group. The EIB group had higher baseline ENO values (12.3 +/- 1.6 ppb) than the healthy children (6.1 +/- 0.2 ppb) (p < 0.01). The time course of ENO was similar in the EIB, non-EIB, and control groups, with no significant changes after exercise (p = NS). In the overall group of asthmatic children there was a significant correlation (r = 0.61, p < 0.01) between baseline (preexercise) ENO and magnitude of the maximal decrease in FEV(1) after exercise. In conclusion, our study shows that ENO levels do not change during acute airway obstruction induced by exercise challenge in asthmatic children. In addition, baseline ENO values correlate with the magnitude of postexercise bronchoconstriction, suggesting that NO may be a predictor of airway hyperresponsiveness to exercise.
The efficacy of the Neonatal Resuscitation Program (NRP) courses was previously evaluated, demons... more The efficacy of the Neonatal Resuscitation Program (NRP) courses was previously evaluated, demonstrating good retention of knowledge in the participants. However, there is a lack of information regarding the participants&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; performance in relation to the different steps of neonatal resuscitation. We aimed to assess the knowledge gained and retained by pediatric residents who participated in a NRP course in relation to the different steps. An 80-item questionnaire derived from the standard test contained in the American Heart Association and American Academy of Pediatrics Neonatal Resuscitation Manual was given to 25 pediatric residents before, immediately after and 6 months after the course. The percentages of correct answers significantly improved from before (37.6 +/- 3.1%) to immediately after the course (94.1 +/- 0.9%) (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The percentages at the 6 months follow-up test (62.7 +/- 2.2%) significantly decreased from posttest (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), but remained significantly higher with respect to pretest performance (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The percentages of correct answers were different among the four neonatal resuscitation steps during the entire study (pretest, posttest and follow-up test). The knowledge gained by pediatric residents participating in the NRP course was very high, but was only partially retained over time. In particular, it was different among the four steps of neonatal resuscitation suggesting further studies on teaching resuscitation.
Clinical chemistry, 1998
We describe a new HPLC method for the simultaneous determination of lactulose and mannitol in uri... more We describe a new HPLC method for the simultaneous determination of lactulose and mannitol in urine, in which cation-exchange chromatography and evaporative light-scattering detection are used. The two sugars are orally administered for the estimation of intestinal permeability in children. Samples were purified by solid phase extraction on a C18 cartridge and subsequent addition of anion-exchange resin. Cellobiose may be used as an internal standard. The chromatographic separation was carried out in 16 min at a flow rate of 0.5 mL/min, using deionized water as the mobile phase. Within-run precision (CV) measured at three concentrations was 1.6-2.3% for lactulose and 1.0-1.9% for mannitol. Between-run CVs were 2.1-4.1% and 1.3-2.7% for lactulose and mannitol, respectively. Analytical recovery of both sugar probes was 97-101%. The detection limits (signal-to-noise ratio = 3) were 0.82 mg/L for lactulose and 0.65 mg/L for mannitol. The lactulose/ mannitol ratio in control subjects was...
Pediatric Pulmonology, 1998
The measurement of exhaled nitric oxide concentrations [NO] may provide a simple, noninvasive mea... more The measurement of exhaled nitric oxide concentrations [NO] may provide a simple, noninvasive means for measuring airway inflammation. However, several measurement conditions may influence exhaled NO levels, and ambient NO may be one of these. We measured exhaled NO levels in 47 stable asthmatic children age 5 to 17 years and in 47 healthy children, gender and age matched. Exhaled [NO] in expired air was measured by a tidal breathing method with a chemiluminescence analyzer, sampling at the expiratory side of the mouthpiece. NO steady-state levels were recorded. In order to keep the soft palate closed and avoid nasal contamination, the breathing circuit had a restrictor providing an expiratory pressure of 3-4 cm H 2 O at the mouthpiece. To evaluate the effect of [NO] in ambient air, measurements were randomly performed by breathing ambient air or NO-free air from a closed circuit.
Pediatric Neurology, 2005
This report presents the long-term (36 months) neurologic outcome in 12 neonates and 9 children w... more This report presents the long-term (36 months) neurologic outcome in 12 neonates and 9 children who survived after extracorporeal membrane oxygenation and attempts to identify its prognostic indicators through a prospective study in the pediatric intensive care unit of a university hospital. Outcome assessment, neurodevelopmental tests, electroencephalogram, auditory evoked potentials, visual evoked potentials, and somatosensory evoked potentials, cerebral sonography, or cerebral tomography were evaluated at the end of bypass and at 6, 12, 24, and 36 months after extracorporeal membrane oxygenation. "Before extracorporeal membrane oxygenation" variables (oxygenation index, pH, oxygen arterial partial pressure) and "during extracorporeal membrane oxygenation" variables (pH, oxygen arterial partial pressure, duration of bypass, clotting activated time, electroencephalogram) were also analyzed. A negative neurologic outcome (Glasgow Outcome Score different from "good recovery" or neurodevelopmental score less than 70) 12 months after extracorporeal membrane oxygenation was documented in 8.3% of neonates and in 30% of children who survived. There was no further change in subsequent evaluations (24 and 36 months follow-up). The most abnormal electroencephalogram during extracorporeal membrane oxygenation, the first electroencephalogram, neuroimaging score, and somatosensory evoked potentials after extracorporeal membrane oxygenation treatment were associated with negative neurologic outcome. The study documented that neonates and children treated with extracorporeal membrane oxygenation require long-term follow-up; electroencephalogram, neuroimaging score, and somatosensory evoked potentials have prognostic value for abnormal neurologic outcome.
The Lancet, 1988
Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled... more Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled vocabulary for indexing life sciences content.< br/> Note that some records do not have MeSH. These include Patents and the latest PubMed and PubMed Central records.
Journal of Pediatric Gastroenterology and Nutrition, 1990
Unlike adults (greater than 60% of cases), it is rare to find the chronic hepatitis B virus (HBV)... more Unlike adults (greater than 60% of cases), it is rare to find the chronic hepatitis B virus (HBV) carrier status with normal transaminases among children. The aim of this study was to investigate whether this status would depend on the duration of HBV infection, that is, whether chronic hepatitis in childhood would lead to the asymptomatic carrier status in later life. We reexamined all of our patients with chronic HBV infection of greater than 10 years' duration and with histologically documented chronic hepatitis during childhood. This was a group of 36 adolescents and young adults. All subjects were screened for tumor using alpha-fetoprotein assay and hepatic ultrasound. Eight patients with cirrhosis underwent esophageal fiberoptic endoscopy. All patients were in good general condition, with no clinical signs of liver failure. Only two patients had abnormal transaminase levels, both of whom had evidence of delta infection. All but one patient became anti-HBe positive. Five cases had HBsAg clearance. (Seventy-one percent of patients were HBeAg positive and 14% anti-HBe positive at the onset of the disease.) Hepatic ultrasound revealed no tumors in any of the subjects, and fiberoptic endoscopy demonstrated no esophageal varices. This study suggests that (a) chronic hepatitis and asymptomatic carrier status may be subsequent stages of the B virus infection; and (b) chronic hepatitis in childhood is generally benign and may evolve into an asymptomatic carrier status. The main problem with the chronic carrier status is probably the increased risk of hepatocellular carcinoma.
Intensive Care Medicine, 1996
Introduction: Permissive hypercapnia (PH) is a beneficial strategy for patients with acute respir... more Introduction: Permissive hypercapnia (PH) is a beneficial strategy for patients with acute respiratory distress syndrome (ARDS) to minimize barotrauma by decreasing the peak inspiratory pressure (PIP). Hypercapnia and hypoxia cause pulmonary vasoconstriction, pulmonary artery (PA) hypertension, and, thus, an increased afterload to the right ventricle. This increased afterload may result in increased right ventricular (RV) work load and subsequent RV dysfunction. One therapeutic approach is the use of inhaled nitric oxide (iNO), a selective PA vasodilator. The objectives of this study were to test the hypothesis that in a swine model of ARDS with PH, iNO would improve RV work load and not change intrinsic RV contractility.
European Respiratory Journal, 1998
European Journal of Pediatrics, 1997
We followed the clinical course of 21 infants with bronchopulmonary dysplasia enrolled in a prosp... more We followed the clinical course of 21 infants with bronchopulmonary dysplasia enrolled in a prospective home O2 therapy programme during a 4-year-period. Mean gestational age was 28.5 weeks (range, 25-36 weeks) and mean birth weight 1093 g (range 630-2750 g). Infants were regularly monitored to maintain pulse oximeter O2 saturation over 94%-95%. The source of O2 was liquid oxygen and was delivered by nasal cannula. During the follow up oxygenation was assessed by SatO2 measurement, cardiac function by Doppler echocardiography and respiratory function by the occlusion technique. All patients had an ophthalmological follow up. The mean age of the infants at discharge was 3.7 months (range 1.7-8.6) and mean weight 2830 g (range 2150-3780 g). At discharge 8 infants had right ventricular hypertrophy (RVH) and four of them had pulmonary hypertension. Mean duration of home O2 therapy was 97 days (range 15-320 days) and the mean age of discontinuation of O2 was 6.9 months (range 3-14.7 months). The cardiological follow up was benign: the ECG signs of RVH disappeared by 12 months of age in six out of eight infants and the right ventricular pulmonary pressure, as measured by the Doppler method, normalised in the four patients in whom it was detected. No relationship was found between respiratory mechanics and the duration of O2 therapy. Weight gain was poor with mean growth at the 3rd percentile for females and just below the 3rd percentile for males. Twelve of the 21 infants required 25 rehospitalizations. No one presented deterioration of retinopathy of prematurity that was present in 16 infants at discharge; at 12 months retinopathy was resolved in 14 infants. A total of 2025 hospital days were saved, representing a significant financial saving. Home O2 therapy permits the safe early discharge of O2-dependent BPD infants and it reduces significantly the length of time spent in hospital which represents a considerable financial saving.
European Journal of Pediatrics, 1994
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common inherited disorder of mi... more Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common inherited disorder of mitochondrial fatty acid b-oxidation in humans. To better understand the pathogenesis of this disease, we developed a mouse model for MCAD deficiency (MCAD À/À ) by gene targeting in embryonic stem (ES) cells. The MCAD À/À mice developed an organic aciduria and fatty liver, and showed profound cold intolerance at 4 8C with prior fasting. The sporadic cardiac lesions seen in MCAD À/À mice have not been reported in human MCAD patients. There was significant neonatal mortality of MCAD À/À pups demonstrating similarities to patterns of clinical episodes and mortality in MCAD-deficient patients. The MCAD-deficient mouse reproduced important aspects of human MCAD deficiency and is a valuable model for further analysis of the roles of fatty acid oxidation and pathogenesis of human diseases involving fatty acid oxidation. Citation: Tolwani RJ, Hamm DA, Tian L, Sharer JD, Vockley J, et al. (2005) Medium-chain acyl-CoA dehydrogenase deficiency in gene-targeted mice. PLoS Genet 1(2): e23.
European Journal of Cancer, 1998
We conducted a mutation analysis of the most conserved region of the neurofibromatosis type 1 (NF... more We conducted a mutation analysis of the most conserved region of the neurofibromatosis type 1 (NF1) gene, the guanine triphosphatase (GTPase) activating protein (GAP)-related domain (NF1 GRD), to which the function of tumour suppressor is attributed. Sixty primary neuroectodermal tumours were analysed. The rationale for the study was based on the likelihood of finding structural alterations resulting in loss of function of this region in tumours of neuroepithelial tissues, where the activity of neurofibromin seems to be crucial in regulating the mechanisms of signal transduction and cell transformation mediated by p21 ras. Following analysis of the whole NF1 GRD sequence, no mutations were identified in the tumours analysed. We conclude that the loss of NF1 gene tumour suppressor function, that might lead or contribute to the development of malignancies in neuroectodermal tissues, is not due to structural abnormalities of the region of the gene which interacts with p21 ras.
A nonradioactive in situ hybridization technique was utilized for the rapid and early diagnosis o... more A nonradioactive in situ hybridization technique was utilized for the rapid and early diagnosis of cytomegalovirus (CMV) infection in children undergoing kidney transplantation. The cellular samples were obtained directly from the organs thought to be affected on the basis of clinical findings: bronchoalveolar lavage during interstitial pneumonia (7 samples from 6 cases); fine-needle aspiration biopsy (FNAB) of the liver during acute hepatitis (1 case); kidney FNAB and peripheral blood where there was a greater than or equal to 25% creatinine rise with or without fever (26 episodes). Standard virus isolation procedures and an immunofluorescent technique on short-term cultures of human fibroblast cells were performed as a control. 6/23 children followed had a symptomatic CMV infection (4 had interstitial pneumonia; 1 had acute hepatitis, and there was 1 case of creatinine rise with fever). In all cases, the diagnosis was provided by in situ hybridization in less than 24 h. These results were confirmed 48 h later by immunofluorescence and after 5-25 days by standard viral cultures. In situ hybridization with a biotinylated probe proved to be a rapid and sensitive method for diagnosis of CMV disease, when performed on specimens obtained from the involved organs at an early stage of the infection. This diagnostic approach allowed a specific antiviral therapy to be undertaken promptly.
American Journal of Respiratory and Critical Care Medicine, 1997
Recently, it has been demonstrated that paranasal sinuses are an important site of nitric oxide (... more Recently, it has been demonstrated that paranasal sinuses are an important site of nitric oxide (NO) production in the upper airways. The aim of this study was to evaluate the NO nasal concentration in children with acute maxillary sinusitis before and after treatment with antibiotic therapy. We performed NO nasal measurements in 16 children 4 to 13 yr of age with acute maxillary sinusitis and compared values with 16 age-and sex -matched healthy control subjects. The diagnosis of acute sinusitis was done by clinical signs and symptoms in addition to radiographic examination. NO nasal concentrations were measured by a chemiluminescence analyzer. Nasal NO steady state during oral breathing was recorded. The mean ± SEM NO nasal concentration in children with sinusitis was 70 8.7 parts per billion (ppb) and increased significantly to 220 ± 15 ppb (p < 0.001) after antibiotic therapy (amoxicillin/clavulanate). NO values after recovery from sinusitis were similar to those of healthy control subjects (245 ± 15 ppb, p = NS). NO nasal measurements were also performed before and after antibiotic treatment in nine children 4 to 12 yr of age with symptoms of upper respiratory tract infection but no symptoms of sinusitis. In these children NO nasal levels were 249 ± 32 ppb and did not change (p = NS) after antibiotic therapy. We conclude that during acute maxillary sinusitis the concentration of nasal NO is largely decreased, probably because of an impaired flow of NO from the paranasal sinuses, and that NO returns to normal levels after antibiotic therapy. Baraldi E, Azzolin NM, Biban P, Zacchello F. Effect of antibiotic therapy on nasal nitric oxide concentration In children with acute sinusitis AM J RESPIR CRIT CARE MED 1997;155:1680-1683.
American Journal of Respiratory and Critical Care Medicine, 2000
It is known that exhaled nitric oxide (ENO) is increased in asthmatic individuals, probably as an... more It is known that exhaled nitric oxide (ENO) is increased in asthmatic individuals, probably as an expression of airway inflammation, but no studies have been reported of ENO and exercise-induced bronchoconstriction (EIB). We assessed the effect of a treadmill exercise challenge on ENO concentration in 24 asthmatic children aged 11.2 +/- 0.4 yr (mean +/- SEM). According to the presence or absence of EIB, the children were divided into an EIB group (n = 10) and a non-EIB group (n = 14). ENO was measured with a single-breath reservoir technique. FEV(1), ENO, and heart rate were measured at baseline and 1, 6, 12, and 18 min after the end of exercise. We also measured ENO in 18 healthy control children aged 10.8 +/- 0.6 yr, of whom nine underwent an exercise challenge identical to that of the asthmatic children. After the exercise test, the mean decrease in FEV(1) was 34% in the EIB group and 5% in the non-EIB group. The EIB group had higher baseline ENO values (12.3 +/- 1.6 ppb) than the healthy children (6.1 +/- 0.2 ppb) (p < 0.01). The time course of ENO was similar in the EIB, non-EIB, and control groups, with no significant changes after exercise (p = NS). In the overall group of asthmatic children there was a significant correlation (r = 0.61, p < 0.01) between baseline (preexercise) ENO and magnitude of the maximal decrease in FEV(1) after exercise. In conclusion, our study shows that ENO levels do not change during acute airway obstruction induced by exercise challenge in asthmatic children. In addition, baseline ENO values correlate with the magnitude of postexercise bronchoconstriction, suggesting that NO may be a predictor of airway hyperresponsiveness to exercise.
The efficacy of the Neonatal Resuscitation Program (NRP) courses was previously evaluated, demons... more The efficacy of the Neonatal Resuscitation Program (NRP) courses was previously evaluated, demonstrating good retention of knowledge in the participants. However, there is a lack of information regarding the participants&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; performance in relation to the different steps of neonatal resuscitation. We aimed to assess the knowledge gained and retained by pediatric residents who participated in a NRP course in relation to the different steps. An 80-item questionnaire derived from the standard test contained in the American Heart Association and American Academy of Pediatrics Neonatal Resuscitation Manual was given to 25 pediatric residents before, immediately after and 6 months after the course. The percentages of correct answers significantly improved from before (37.6 +/- 3.1%) to immediately after the course (94.1 +/- 0.9%) (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The percentages at the 6 months follow-up test (62.7 +/- 2.2%) significantly decreased from posttest (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), but remained significantly higher with respect to pretest performance (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The percentages of correct answers were different among the four neonatal resuscitation steps during the entire study (pretest, posttest and follow-up test). The knowledge gained by pediatric residents participating in the NRP course was very high, but was only partially retained over time. In particular, it was different among the four steps of neonatal resuscitation suggesting further studies on teaching resuscitation.