European Journal of Hospital Pharmacy: Science and Practice, 2015
Background A frail patient is an immobilised person and/or a nursing home resident and/or in a te... more Background A frail patient is an immobilised person and/or a nursing home resident and/or in a terminal stage. This population is hyper-frequent in primary health care (PHC) centres and hospitals. This group generates large expenses in drugs and they usually need a nasogastric tube (NGT). Purpose To evaluate the implementation of pharmacy assistance for frail patients with NGT after hospital discharge. Material and methods Prospective study conducted between June and September 2014. Sequence of activities: a physician or nurse selected the patients who require pharmaceutical intervention to guarantee the correct administration of drugs via NGT, compatibility with enteral nutrition and stability of solid solutions or dispersions of drugs. A report with recommendations, substitutions and interruptions of treatments was issued to the patient. Variables: age, drugs per patient, therapeutic group (TG) according to the Anatomical Therapeutic Chemical (ATC) classification system and active substances with submitted recommendations and levels of approval. Sources of information: electronic medical history (DIRAYA), electronic prescription program (APD – ATHOS) and specialised bibliography. Data was analysed using SPSS 15.0. Results 23 requests were received. The mean age of the patients was 81.65 (± 8.97) years. The mean of prescribed drugs per patient was 8 (2–19). 75% (138/184) of the patients required specific recommendations (a mean of 6 drugs per patient). The most common TGs were related to the nervous system 29.71% (41) and the cardiovascular system 25.36% (35). The most frequent active principles were: omeprazole 9.42% (13) and acetylsalicylic acid 5.8% (8). 100% of the recommendations were accepted. Conclusion This system guarantees a constant information flow between PHC centres and hospitals that will avoid problems and guarantee correct drug administration. Future studies will show the economic impact and the improvement in the quality of life with the reduction of visits to PHC centres and hospitals. References and/or Acknowledgements None. No conflict of interest.
Journal of Pediatric Endocrinology and Metabolism, 2010
Congenital hyperinsulinism (CHI) is responsible for profound hypoglycaemia which needs aggressive... more Congenital hyperinsulinism (CHI) is responsible for profound hypoglycaemia which needs aggressive treatment in order to prevent neurological damage. Mutations in seven different genes have been held responsible for the inappropriate insulin secretion, typical of this condition. The most common cause of CHI is autosomal recessive mutations in the ABCC8 and KCNJ11 genes which encode for two subunits (SUR 1 and Kir6.2, respectively) of the pancreatic B-cell ATP-sensitive potassium channel. Furthermore, histopathological lesions, diffuse and focal, have been associated with different genetic alterations. [18F]Fluorodopa PET/CT imaging, in most cases, differentiates focal from diffuse disease and is 100% accurate in localizing the focal lesion. Recently laparoscopic pancreatectomy has been performed and is curative in the focal form. We report a case in which clinical experience together with rapid genetic analysis, imaging with 18F-DOPA-PET/CT and laparoscopic surgery, were able to guide the correct clinical management of this condition.
Despite recent advances in the perinatal management of neonatal respiratory distress syndrome (RD... more Despite recent advances in the perinatal management of neonatal respiratory distress syndrome (RDS), controversies still exist. We report the recommendations of a Euro-*In cooperation with the Working Group on Prematurity of the World Association of Perinatal Medicine and endorsed by the European Association of Perinatal Medicine.
The use of magnesium sulfate (MgSO 4) in European obstetric units is unknown. We aimed to describ... more The use of magnesium sulfate (MgSO 4) in European obstetric units is unknown. We aimed to describe reported policies and actual use of MgSO 4 in women delivering before 32 weeks of gestation by indication. Methods: We used data from the European Perinatal Intensive Care in Europe (EPICE) population-based cohort study of births before 32 weeks of gestation in 19 regions in 11 European countries. Data were collected from April 2011 to September 2012 from medical records and questionnaires. The study population comprised 720 women with severe preeclampsia, eclampsia or HELLP and 3658 without preeclampsia delivering from 24 to 31 weeks of gestation in 119 maternity units with 20 or more very preterm deliveries per year. Results: Among women with severe pre-eclampsia, eclampsia or HELLP, 255 (35.4%) received MgSO 4 before delivery. 41% of units reported use of MgSO 4 whenever possible for pre-eclampsia and administered MgSO 4 more often than units reporting use sometimes. In women without pre-eclampsia, 95 (2.6%) received MgSO 4. 9 units (7.6%) reported using MgSO 4 for fetal neuroprotection whenever possible. In these units, the median rate of MgSO 4 use for deliveries without severe pre-eclampsia, eclampsia and HELLP was 14.3%. Only 1 unit reported using MgSO 4 as a first-line tocolytic. Among women without preeclampsia, MgSO 4 use was not higher in women hospitalised before delivery for preterm labour. Conclusions: Severe pre-eclampsia, eclampsia or HELLP are not treated with MgSO 4 as frequently as evidence-based medicine recommends. MgSO 4 is seldom used for fetal neuroprotection, and is no longer used for tocolysis. To continuously lower morbidity, greater attention to use of MgSO 4 is needed.
Advance in the science and technology of neonatal and pediatric critical care have resulted in im... more Advance in the science and technology of neonatal and pediatric critical care have resulted in improved outcome for high risk newborn and children. Effective interhospital transport programmes are necessary for the appropriate use of resources and has become an integral component of regionalized perinatal care. It is now well established that use of an organized neonatal and pediatric transport team results in a fall in mortality and morbidity of infant. The American College of Obstetrician and Gynecologist and, recently, American Academy of Pediatrics published guidelines and recommendations for safe interhospital transfer of neonates, infants and children. Training of personnel, selection of equipment, organization and communication between hospitals are critical elements of a successful transport system. We present an overview of the role, principles and operating procedures of such neonatal-pediatric transport team and the basis of clinical stabilization before and during transfer. We also discuss data of the first 17 month experience of the Neonatal-Pediatric Transport Service of the Department of Pediatrics, University of Padua
BACKGROUND: In preterm infants, InSurE (Intubation-Surfactant-Extubation) and LISA (less invasive... more BACKGROUND: In preterm infants, InSurE (Intubation-Surfactant-Extubation) and LISA (less invasive surfactant administration) techniques allow for exogenous surfactant administration while reducing lung injury associated with mechanical ventilation. We compared the acute pulmonary response and lung deposition of surfactant by LISA and InSurE in surfactant-depleted adult rabbits. METHODS: Twenty-six spontaneously breathing surfactant-depleted adult rabbits (6-7 weeks old) with moderate RDS and managed with nasal continuous positive airway pressure were randomized to 3 groups: (1) 200 mg/kg of surfactant by InSurE; (2) 200 mg/kg of surfactant by LISA; (3) no surfactant treatment (Control). Gas exchange and lung mechanics were monitored for 180 min. After that, surfactant lung deposition and distribution were evaluated monitoring disaturated-phosphatidylcholine (DSPC) and surfactant protein C (SP-C), respectively. RESULTS: No signs of recovery were found in the untreated animals. After InSurE, oxygenation improved more rapidly compared to LISA. However, at 180' LISA and InSurE showed comparable outcomes in terms of gas exchange, ventilation parameters, and lung mechanics. Neither DSPC in the alveolar pool nor SP-C signal distributions in a frontal lung section were significantly different between InSurE and LISA groups. CONCLUSIONS: In an acute setting, LISA demonstrated efficacy and surfactant lung delivery similar to that of InSurE in surfactantdepleted adult rabbits.
OBJECTIVE: The goal was to study exogenous surfactant disaturated phosphatidylcholine (DSPC) kine... more OBJECTIVE: The goal was to study exogenous surfactant disaturated phosphatidylcholine (DSPC) kinetics in preterm infants with respiratory distress syndrome (RDS) who were treated with 100 or 200 mg/kg porcine surfactant. METHODS: Sixty-one preterm infants with RDS undergoing mechanical ventilation received, within 24 hours after birth, 100 mg/kg (N = 40) or 200 mg/kg (N = 21) porcine surfactant mixed with [U-13C]dipalmitoylphosphatidylcholine. Clinical and respiratory parameters were recorded, and DSPC half-life and pool size and endogenous DSPC synthesis rate were calculated. RESULTS: Clinical characteristics and short-term outcomes did not differ between groups. In the 100 mg/kg group, 28 infants (70%) received a second dose after 25 ± 11 hours and 9 (22.5%) a third dose after 41 ± 11 hours; in the 200 mg/kg group, 6 infants (28.6%) received a second dose after 33 ± 8 hours and 1 a third dose. The DSPC half-life was longer in the 200 mg/kg group (first dose: 32 ± 19 vs 15 ± 15 hou...
Background: Nurses in Pediatric Intensive Care Units (PICU) are daily exposed to the suffering an... more Background: Nurses in Pediatric Intensive Care Units (PICU) are daily exposed to the suffering and death of their patients. Often the emotional burden may become unbereable, dysfunctional responses may arise and reflect negatively on patients' care.
The aim of the study was to measure for the first time in humans surfactant disaturated-phosphati... more The aim of the study was to measure for the first time in humans surfactant disaturated-phosphatidylcholine (DSPC) net synthesis and kinetics by using a novel, dual stable isotope tracer approach. Ten infants with congenital diaphragmatic hernia [CDH; birth weight, 3.4 Ϯ 0.2; gestational age, 39.8 Ϯ 0.4 wk] and 6 age-matched control subjects with no lung disease (birth weight, 3.2 Ϯ 0.3 kg; gestational age, 39.1 Ϯ 1.1 wk), all of whom were admitted to the neonatal intensive care unit (Padua, Italy), were studied. All infants received simultaneously an intratracheal (carbon-13 dipalmitoyl-phosphatidylcholine) and an i.v. (deuterated palmitic acid) stable isotope tracer. Isotopic enrichment curves of DSPC from sequential tracheal aspirates were analyzed by mass spectrometry. DSPC kinetic data were expressed as mean Ϯ SEM and compared by the Mann-Whitney test. DSPC net synthesis from plasma palmitate was nearly identical in infants with CDH and control subjects (8.6 Ϯ 2.2 and 8.1 Ϯ 1.5 mg • kg Ϫ1 • d Ϫ1 ; P ϭ 0.7). DSPC apparent pool size was 36.7 Ϯ 7.5 and 58.5 Ϯ 9.1 mg/kg (P ϭ 0.07) and half-life was 26.7 Ϯ 4.5 and 50.3 Ϯ 9.7 h (P ϭ 0.03) in infants with CDH and control subjects, respectively. Both DSPC turnover and percentage of catabolism/recycling significantly correlated with duration of mechanical ventilation. In conclusion, the measurements of net DSPC synthesis and catabolism/recycling were reported for the first time in humans. Mean net DSPC synthesis was~8 mg • kg Ϫ1 • d Ϫ1. No significant differences were found between control subjects and infants with CDH. DSPC turnover was faster in infants with CDH, presumably reflecting an increased DSPC catabolism/recycling. Whether this may ultimately lead to a secondary surfactant deficiency in infants with CDH is still to be ascertained. (Pediatr Res 56: 184-190, 2004) Abbreviations CDH, congenital diaphragmatic hernia DPPC, di-palmitoyl-phosphatidylcholine DSPC, disaturated-phosphatidylcholine ECMO, extracorporeal membrane oxygenation FIO 2 , fraction of inspired oxygen FSR, fractional synthesis rate P A O 2 , alveolar oxygen pressure PaO 2 , arterial oxygen pressure SPA , surfactant protein A
Aspiration pneumonitis can lead to alveolar surfactant dysfunction. We employed a murine model of... more Aspiration pneumonitis can lead to alveolar surfactant dysfunction. We employed a murine model of unilateral aspiration to compare surfactant synthesis in the injured (I) and noninjured (NI) contralateral lung. Mice were instilled with hydrochloric acid in the right bronchus and, after 18 h, an intraperitoneal dose of deuterated water was administered as precursor of disaturated phosphatidylcholine (DSPC)-palmitate. Selected bronchoalveolar lavage fluid (BALF) was collected at scheduled time points and lungs were removed. We measured DSPC-palmitate synthesis in lung tissue and secretion in BALF by gas chromatography-isotope ratio mass spectrometry, together with total proteins and myeloperoxidase activity (MPO) by spectrophotometry. BALF total proteins and MPO were significantly increased in the I lungs compared with NI and naïve control lungs. The DSPC pool size was significantly lower in the BALF of the I lungs compared with naïve controls. DSPC synthesis was accelerated in the I ...
American Journal of Respiratory and Critical Care Medicine, 2000
Little is known about surfactant metabolism in newborn infants, since radioactive isotopes cannot... more Little is known about surfactant metabolism in newborn infants, since radioactive isotopes cannot be used in humans. We describe here a new method for studying exogenous surfactant pharmacokinetics in vivo. We measured surfactant half-life, pool size, and turnover time in eight preterm infants (gestational age: 30 +/- 2 wk; birth weight: 1,416 +/- 202 g) who were mechanically ventilated because of infant respiratory distress syndrome. We administered two doses of 100 mg/kg each of a natural porcine surfactant with (13)C-labeled dipalmitoylphosphatidylcholine as a tracer. The (13)C enrichment of surfactant disaturated phosphatidylcholine (DSPC) was measured in serial tracheal aspirates by gas chromatography-mass spectrometry. The DSPC half-life was 34.2 +/- 9.4 h (mean +/- SD; range: 21.8 to 45.9 h). The apparent DSPC pool sizes were 5.8 +/- 6.1 mg/kg (range: 0.1 to 17.0 mg/kg) and 17.3 +/- 13.6 mg/kg (range: 3.3 to 41.0 mg/kg) at the time of the first and second surfactant doses, respectively. We present a novel and safe method that allows the tracing of exogenous surfactant phosphatidylcholine, the major lipid component of pulmonary surfactant, in infants who receive exogenous surfactant. This method could be a valuable tool for studying: (1) therapies that enhance lung/surfactant maturation; (2) the dosing and timing of surfactant therapy in different lung diseases; and (3) the comparison of different surfactant preparations.
BACKGROUND & AIMS Extra-uterine growth restriction (EUGR) is common among very preterm (VPT) ... more BACKGROUND & AIMS Extra-uterine growth restriction (EUGR) is common among very preterm (VPT) infants and has been associated with impaired neurodevelopment. Some research suggests that adverse effects of EUGR may be more severe in boys. We investigated EUGR and neurodevelopment at 2 years of corrected age (CA) by sex in a VPT birth cohort. METHODS Data come from a population-based cohort of children born <32 weeks' gestation from 11 European countries and followed up at 2 years CA. Postnatal growth during the neonatal hospitalization was measured with: (1) birthweight and discharge-weight Z-score differences using Fenton charts (2) weight-gain velocity using Patel's model. Published cut-offs were used to define EUGR as none, moderate or severe. Neurodevelopmental impairment was assessed using a parent-report questionnaire, with standardized questions/instruments on motor function, vision, hearing and non-verbal cognition. We estimated relative risks (RR) adjusting for maternal and neonatal characteristics overall and by sex. RESULTS Among 4197 infants, the prevalence of moderate to severe impairment at 2 years CA was 17.7%. Severe EUGR was associated with neurodevelopmental impairment in the overall sample and the interaction with sex was significant. For boys, adjusted RR were 1.57 (95% Confidence Intervals (CI): 1.18-2.09) for Fenton's delta Z-score and 1.50 (95% CI: 1.12-2.01) for Patel's weight-gain velocity, while for girls they were 0.97 (0.76-1.22) and 1.12 (0.90-1.40) respectively. CONCLUSION EUGR was associated with poor neurodevelopment at 2 years among VPT boys but not girls. Understanding why boys are more susceptible to the effects of poor growth is needed to develop appropriate healthcare strategies.
Table S1. Baseline and post lung injury (Post-BAL) characteristics of surfactant-depleted adult r... more Table S1. Baseline and post lung injury (Post-BAL) characteristics of surfactant-depleted adult rabbits treated with nasal continuous positive pressure ventilation (nCPAP), with intratracheal surfactant (Inst-SURF), or with different doses of nebulized surfactant (Neb-SURF100, Neb-SURF200, Neb-SURF400, and Neb-SURF600. Figure S1. PrINT cast with silicon-coated nostrils. Figure S2. Nebulizer output assessment. (DOCX 239 kb)
European Journal of Hospital Pharmacy: Science and Practice, 2015
Background A frail patient is an immobilised person and/or a nursing home resident and/or in a te... more Background A frail patient is an immobilised person and/or a nursing home resident and/or in a terminal stage. This population is hyper-frequent in primary health care (PHC) centres and hospitals. This group generates large expenses in drugs and they usually need a nasogastric tube (NGT). Purpose To evaluate the implementation of pharmacy assistance for frail patients with NGT after hospital discharge. Material and methods Prospective study conducted between June and September 2014. Sequence of activities: a physician or nurse selected the patients who require pharmaceutical intervention to guarantee the correct administration of drugs via NGT, compatibility with enteral nutrition and stability of solid solutions or dispersions of drugs. A report with recommendations, substitutions and interruptions of treatments was issued to the patient. Variables: age, drugs per patient, therapeutic group (TG) according to the Anatomical Therapeutic Chemical (ATC) classification system and active substances with submitted recommendations and levels of approval. Sources of information: electronic medical history (DIRAYA), electronic prescription program (APD – ATHOS) and specialised bibliography. Data was analysed using SPSS 15.0. Results 23 requests were received. The mean age of the patients was 81.65 (± 8.97) years. The mean of prescribed drugs per patient was 8 (2–19). 75% (138/184) of the patients required specific recommendations (a mean of 6 drugs per patient). The most common TGs were related to the nervous system 29.71% (41) and the cardiovascular system 25.36% (35). The most frequent active principles were: omeprazole 9.42% (13) and acetylsalicylic acid 5.8% (8). 100% of the recommendations were accepted. Conclusion This system guarantees a constant information flow between PHC centres and hospitals that will avoid problems and guarantee correct drug administration. Future studies will show the economic impact and the improvement in the quality of life with the reduction of visits to PHC centres and hospitals. References and/or Acknowledgements None. No conflict of interest.
Journal of Pediatric Endocrinology and Metabolism, 2010
Congenital hyperinsulinism (CHI) is responsible for profound hypoglycaemia which needs aggressive... more Congenital hyperinsulinism (CHI) is responsible for profound hypoglycaemia which needs aggressive treatment in order to prevent neurological damage. Mutations in seven different genes have been held responsible for the inappropriate insulin secretion, typical of this condition. The most common cause of CHI is autosomal recessive mutations in the ABCC8 and KCNJ11 genes which encode for two subunits (SUR 1 and Kir6.2, respectively) of the pancreatic B-cell ATP-sensitive potassium channel. Furthermore, histopathological lesions, diffuse and focal, have been associated with different genetic alterations. [18F]Fluorodopa PET/CT imaging, in most cases, differentiates focal from diffuse disease and is 100% accurate in localizing the focal lesion. Recently laparoscopic pancreatectomy has been performed and is curative in the focal form. We report a case in which clinical experience together with rapid genetic analysis, imaging with 18F-DOPA-PET/CT and laparoscopic surgery, were able to guide the correct clinical management of this condition.
Despite recent advances in the perinatal management of neonatal respiratory distress syndrome (RD... more Despite recent advances in the perinatal management of neonatal respiratory distress syndrome (RDS), controversies still exist. We report the recommendations of a Euro-*In cooperation with the Working Group on Prematurity of the World Association of Perinatal Medicine and endorsed by the European Association of Perinatal Medicine.
The use of magnesium sulfate (MgSO 4) in European obstetric units is unknown. We aimed to describ... more The use of magnesium sulfate (MgSO 4) in European obstetric units is unknown. We aimed to describe reported policies and actual use of MgSO 4 in women delivering before 32 weeks of gestation by indication. Methods: We used data from the European Perinatal Intensive Care in Europe (EPICE) population-based cohort study of births before 32 weeks of gestation in 19 regions in 11 European countries. Data were collected from April 2011 to September 2012 from medical records and questionnaires. The study population comprised 720 women with severe preeclampsia, eclampsia or HELLP and 3658 without preeclampsia delivering from 24 to 31 weeks of gestation in 119 maternity units with 20 or more very preterm deliveries per year. Results: Among women with severe pre-eclampsia, eclampsia or HELLP, 255 (35.4%) received MgSO 4 before delivery. 41% of units reported use of MgSO 4 whenever possible for pre-eclampsia and administered MgSO 4 more often than units reporting use sometimes. In women without pre-eclampsia, 95 (2.6%) received MgSO 4. 9 units (7.6%) reported using MgSO 4 for fetal neuroprotection whenever possible. In these units, the median rate of MgSO 4 use for deliveries without severe pre-eclampsia, eclampsia and HELLP was 14.3%. Only 1 unit reported using MgSO 4 as a first-line tocolytic. Among women without preeclampsia, MgSO 4 use was not higher in women hospitalised before delivery for preterm labour. Conclusions: Severe pre-eclampsia, eclampsia or HELLP are not treated with MgSO 4 as frequently as evidence-based medicine recommends. MgSO 4 is seldom used for fetal neuroprotection, and is no longer used for tocolysis. To continuously lower morbidity, greater attention to use of MgSO 4 is needed.
Advance in the science and technology of neonatal and pediatric critical care have resulted in im... more Advance in the science and technology of neonatal and pediatric critical care have resulted in improved outcome for high risk newborn and children. Effective interhospital transport programmes are necessary for the appropriate use of resources and has become an integral component of regionalized perinatal care. It is now well established that use of an organized neonatal and pediatric transport team results in a fall in mortality and morbidity of infant. The American College of Obstetrician and Gynecologist and, recently, American Academy of Pediatrics published guidelines and recommendations for safe interhospital transfer of neonates, infants and children. Training of personnel, selection of equipment, organization and communication between hospitals are critical elements of a successful transport system. We present an overview of the role, principles and operating procedures of such neonatal-pediatric transport team and the basis of clinical stabilization before and during transfer. We also discuss data of the first 17 month experience of the Neonatal-Pediatric Transport Service of the Department of Pediatrics, University of Padua
BACKGROUND: In preterm infants, InSurE (Intubation-Surfactant-Extubation) and LISA (less invasive... more BACKGROUND: In preterm infants, InSurE (Intubation-Surfactant-Extubation) and LISA (less invasive surfactant administration) techniques allow for exogenous surfactant administration while reducing lung injury associated with mechanical ventilation. We compared the acute pulmonary response and lung deposition of surfactant by LISA and InSurE in surfactant-depleted adult rabbits. METHODS: Twenty-six spontaneously breathing surfactant-depleted adult rabbits (6-7 weeks old) with moderate RDS and managed with nasal continuous positive airway pressure were randomized to 3 groups: (1) 200 mg/kg of surfactant by InSurE; (2) 200 mg/kg of surfactant by LISA; (3) no surfactant treatment (Control). Gas exchange and lung mechanics were monitored for 180 min. After that, surfactant lung deposition and distribution were evaluated monitoring disaturated-phosphatidylcholine (DSPC) and surfactant protein C (SP-C), respectively. RESULTS: No signs of recovery were found in the untreated animals. After InSurE, oxygenation improved more rapidly compared to LISA. However, at 180' LISA and InSurE showed comparable outcomes in terms of gas exchange, ventilation parameters, and lung mechanics. Neither DSPC in the alveolar pool nor SP-C signal distributions in a frontal lung section were significantly different between InSurE and LISA groups. CONCLUSIONS: In an acute setting, LISA demonstrated efficacy and surfactant lung delivery similar to that of InSurE in surfactantdepleted adult rabbits.
OBJECTIVE: The goal was to study exogenous surfactant disaturated phosphatidylcholine (DSPC) kine... more OBJECTIVE: The goal was to study exogenous surfactant disaturated phosphatidylcholine (DSPC) kinetics in preterm infants with respiratory distress syndrome (RDS) who were treated with 100 or 200 mg/kg porcine surfactant. METHODS: Sixty-one preterm infants with RDS undergoing mechanical ventilation received, within 24 hours after birth, 100 mg/kg (N = 40) or 200 mg/kg (N = 21) porcine surfactant mixed with [U-13C]dipalmitoylphosphatidylcholine. Clinical and respiratory parameters were recorded, and DSPC half-life and pool size and endogenous DSPC synthesis rate were calculated. RESULTS: Clinical characteristics and short-term outcomes did not differ between groups. In the 100 mg/kg group, 28 infants (70%) received a second dose after 25 ± 11 hours and 9 (22.5%) a third dose after 41 ± 11 hours; in the 200 mg/kg group, 6 infants (28.6%) received a second dose after 33 ± 8 hours and 1 a third dose. The DSPC half-life was longer in the 200 mg/kg group (first dose: 32 ± 19 vs 15 ± 15 hou...
Background: Nurses in Pediatric Intensive Care Units (PICU) are daily exposed to the suffering an... more Background: Nurses in Pediatric Intensive Care Units (PICU) are daily exposed to the suffering and death of their patients. Often the emotional burden may become unbereable, dysfunctional responses may arise and reflect negatively on patients' care.
The aim of the study was to measure for the first time in humans surfactant disaturated-phosphati... more The aim of the study was to measure for the first time in humans surfactant disaturated-phosphatidylcholine (DSPC) net synthesis and kinetics by using a novel, dual stable isotope tracer approach. Ten infants with congenital diaphragmatic hernia [CDH; birth weight, 3.4 Ϯ 0.2; gestational age, 39.8 Ϯ 0.4 wk] and 6 age-matched control subjects with no lung disease (birth weight, 3.2 Ϯ 0.3 kg; gestational age, 39.1 Ϯ 1.1 wk), all of whom were admitted to the neonatal intensive care unit (Padua, Italy), were studied. All infants received simultaneously an intratracheal (carbon-13 dipalmitoyl-phosphatidylcholine) and an i.v. (deuterated palmitic acid) stable isotope tracer. Isotopic enrichment curves of DSPC from sequential tracheal aspirates were analyzed by mass spectrometry. DSPC kinetic data were expressed as mean Ϯ SEM and compared by the Mann-Whitney test. DSPC net synthesis from plasma palmitate was nearly identical in infants with CDH and control subjects (8.6 Ϯ 2.2 and 8.1 Ϯ 1.5 mg • kg Ϫ1 • d Ϫ1 ; P ϭ 0.7). DSPC apparent pool size was 36.7 Ϯ 7.5 and 58.5 Ϯ 9.1 mg/kg (P ϭ 0.07) and half-life was 26.7 Ϯ 4.5 and 50.3 Ϯ 9.7 h (P ϭ 0.03) in infants with CDH and control subjects, respectively. Both DSPC turnover and percentage of catabolism/recycling significantly correlated with duration of mechanical ventilation. In conclusion, the measurements of net DSPC synthesis and catabolism/recycling were reported for the first time in humans. Mean net DSPC synthesis was~8 mg • kg Ϫ1 • d Ϫ1. No significant differences were found between control subjects and infants with CDH. DSPC turnover was faster in infants with CDH, presumably reflecting an increased DSPC catabolism/recycling. Whether this may ultimately lead to a secondary surfactant deficiency in infants with CDH is still to be ascertained. (Pediatr Res 56: 184-190, 2004) Abbreviations CDH, congenital diaphragmatic hernia DPPC, di-palmitoyl-phosphatidylcholine DSPC, disaturated-phosphatidylcholine ECMO, extracorporeal membrane oxygenation FIO 2 , fraction of inspired oxygen FSR, fractional synthesis rate P A O 2 , alveolar oxygen pressure PaO 2 , arterial oxygen pressure SPA , surfactant protein A
Aspiration pneumonitis can lead to alveolar surfactant dysfunction. We employed a murine model of... more Aspiration pneumonitis can lead to alveolar surfactant dysfunction. We employed a murine model of unilateral aspiration to compare surfactant synthesis in the injured (I) and noninjured (NI) contralateral lung. Mice were instilled with hydrochloric acid in the right bronchus and, after 18 h, an intraperitoneal dose of deuterated water was administered as precursor of disaturated phosphatidylcholine (DSPC)-palmitate. Selected bronchoalveolar lavage fluid (BALF) was collected at scheduled time points and lungs were removed. We measured DSPC-palmitate synthesis in lung tissue and secretion in BALF by gas chromatography-isotope ratio mass spectrometry, together with total proteins and myeloperoxidase activity (MPO) by spectrophotometry. BALF total proteins and MPO were significantly increased in the I lungs compared with NI and naïve control lungs. The DSPC pool size was significantly lower in the BALF of the I lungs compared with naïve controls. DSPC synthesis was accelerated in the I ...
American Journal of Respiratory and Critical Care Medicine, 2000
Little is known about surfactant metabolism in newborn infants, since radioactive isotopes cannot... more Little is known about surfactant metabolism in newborn infants, since radioactive isotopes cannot be used in humans. We describe here a new method for studying exogenous surfactant pharmacokinetics in vivo. We measured surfactant half-life, pool size, and turnover time in eight preterm infants (gestational age: 30 +/- 2 wk; birth weight: 1,416 +/- 202 g) who were mechanically ventilated because of infant respiratory distress syndrome. We administered two doses of 100 mg/kg each of a natural porcine surfactant with (13)C-labeled dipalmitoylphosphatidylcholine as a tracer. The (13)C enrichment of surfactant disaturated phosphatidylcholine (DSPC) was measured in serial tracheal aspirates by gas chromatography-mass spectrometry. The DSPC half-life was 34.2 +/- 9.4 h (mean +/- SD; range: 21.8 to 45.9 h). The apparent DSPC pool sizes were 5.8 +/- 6.1 mg/kg (range: 0.1 to 17.0 mg/kg) and 17.3 +/- 13.6 mg/kg (range: 3.3 to 41.0 mg/kg) at the time of the first and second surfactant doses, respectively. We present a novel and safe method that allows the tracing of exogenous surfactant phosphatidylcholine, the major lipid component of pulmonary surfactant, in infants who receive exogenous surfactant. This method could be a valuable tool for studying: (1) therapies that enhance lung/surfactant maturation; (2) the dosing and timing of surfactant therapy in different lung diseases; and (3) the comparison of different surfactant preparations.
BACKGROUND & AIMS Extra-uterine growth restriction (EUGR) is common among very preterm (VPT) ... more BACKGROUND & AIMS Extra-uterine growth restriction (EUGR) is common among very preterm (VPT) infants and has been associated with impaired neurodevelopment. Some research suggests that adverse effects of EUGR may be more severe in boys. We investigated EUGR and neurodevelopment at 2 years of corrected age (CA) by sex in a VPT birth cohort. METHODS Data come from a population-based cohort of children born <32 weeks' gestation from 11 European countries and followed up at 2 years CA. Postnatal growth during the neonatal hospitalization was measured with: (1) birthweight and discharge-weight Z-score differences using Fenton charts (2) weight-gain velocity using Patel's model. Published cut-offs were used to define EUGR as none, moderate or severe. Neurodevelopmental impairment was assessed using a parent-report questionnaire, with standardized questions/instruments on motor function, vision, hearing and non-verbal cognition. We estimated relative risks (RR) adjusting for maternal and neonatal characteristics overall and by sex. RESULTS Among 4197 infants, the prevalence of moderate to severe impairment at 2 years CA was 17.7%. Severe EUGR was associated with neurodevelopmental impairment in the overall sample and the interaction with sex was significant. For boys, adjusted RR were 1.57 (95% Confidence Intervals (CI): 1.18-2.09) for Fenton's delta Z-score and 1.50 (95% CI: 1.12-2.01) for Patel's weight-gain velocity, while for girls they were 0.97 (0.76-1.22) and 1.12 (0.90-1.40) respectively. CONCLUSION EUGR was associated with poor neurodevelopment at 2 years among VPT boys but not girls. Understanding why boys are more susceptible to the effects of poor growth is needed to develop appropriate healthcare strategies.
Table S1. Baseline and post lung injury (Post-BAL) characteristics of surfactant-depleted adult r... more Table S1. Baseline and post lung injury (Post-BAL) characteristics of surfactant-depleted adult rabbits treated with nasal continuous positive pressure ventilation (nCPAP), with intratracheal surfactant (Inst-SURF), or with different doses of nebulized surfactant (Neb-SURF100, Neb-SURF200, Neb-SURF400, and Neb-SURF600. Figure S1. PrINT cast with silicon-coated nostrils. Figure S2. Nebulizer output assessment. (DOCX 239 kb)
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