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Dick Tibboel

Publications and source records attributed to Dick Tibboel.

At least 73 records · Page 4Linked to original sources
PubMed2004

Surfactant replacement therapy on ECMO does not improve outcome in neonates with congenital diaphragmatic hernia.

BACKGROUND PURPOSE: Respiratory failure in neonates with congenital diaphragmatic hernia (CDH) may in part be caused by a primary or secondary surfactant deficiency. Knowledge of the optimal approach to surfactant replacement in neonates with CDH and respiratory failure is limited. The aim of this study was to determine if surfactant replacement on extracorporeal membrane oxygenation (ECMO) results in improved outcomes in neonates > or =35 weeks' gestation with unrepaired CDH. METHODS: Using the CDH Study Group Registry, the authors identified 448 neonates with CDH who were > or =35 weeks' gestation, had no major anomalies, were treated with ECMO within the first 7 days of life, and underwent repair on or after ECMO therapy. Patients in 2 groups were compared: group 1 (- Surf, n = 334) consisted of patients who received no surfactant and group 2 (+ Surf, n = 114) consisted of patients who received at least 1 dose of surfactant while on ECMO. An analysis of all patients in both groups was performed. Additionally, subgroup analyses stratified by gestational age were performed for patients 351/7 to 366/7 weeks' gestation and for patients > or =37 weeks' gestation. Primary end-points for the study were survival and length of ECMO run. Secondary end-points were length of intubation, need for supplemental oxygen at 30 days of life, and at discharge to home. Demographic, clinical, and outcome variables were examined using Fisher's Exact tests for categorical variables and using unpaired t tests for continuous variables. Odds ratios were calculated for categorical end-point variables. RESULTS: Demographic and clinical variables were similar between groups. Analyses of aggregate data showed no significant differences between groups in length of ECMO run, survival, number of days intubated, and percent of patients requiring supplemental oxygen at 30 days or discharge. Subgroup stratification by gestational age did not show significant differences between groups in any of the outcome variables. CONCLUSIONS: The data from this study suggest that surfactant replacement on ECMO for neonates with congenital diaphragmatic hernia does not provide significant benefit in the infant's clinical course with respect to survival, length of ECMO course, length of intubation, or subsequent need for supplemental oxygen.

Extracorporeal Membrane Oxygenation↗
PubMed2004

Malnutrition in critically ill children: from admission to 6 months after discharge.

BACKGROUND & AIMS: Little is known about the nutritional status of critically ill children during hospitalisation in and after discharge from an intensive care unit. We set up a prospective, observational study to evaluate the nutritional status of children in an intensive care unit from admission up to 6 months after discharge. A secondary aim was identifying patient characteristics that influence the course of the various anthropometric parameters. METHODS: The nutritional status of 293 children--104 preterm neonates, 96 term neonates and 93 older children--admitted to our multidisciplinary tertiary pediatric and neonatal intensive care unit was evaluated by anthropometry upon and during admission, at discharge and 6 weeks and 6 months following discharge. RESULTS: Upon admission, 24% of all children appeared to be undernourished. Preterm and term neonates, but not older children, showed a decline in nutritional status during admission. At 6 months after discharge almost all children showed complete recovery of nutritional status. Length of stay and history of disease were the parameters that most adversely affected the nutritional status of preterm and term neonates at discharge and during follow-up. CONCLUSION: While malnutrition is a major problem in pediatric intensive care units, most children have good long-term outcome in terms of nutritional status after discharge.

Adolescent↗
PubMed2004

Splanchnic bed metabolism of glucose in preterm neonates.

BACKGROUND: Glucose is a major oxidative substrate for intestinal energy generation in neonatal animals; however, few data in preterm infants are available. Early administration of enteral nutrition, including glucose, may be an effective strategy to support intestinal adaptation to extrauterine life in preterm neonates. OBJECTIVE: The purpose of the present study was to quantify the first-pass uptake and oxidation of glucose by the splanchnic tissues (intestine and liver) in human neonates. DESIGN: Eight preterm infants [birth weight ( +/- SD): 1.19 +/- 0.22 kg, gestational age: 29 +/- 1 wk] were studied while they received 2 different enteral intakes (A: 40% enteral, 60% parenteral, total glucose intake = 7.5 +/- 0.5 mg. kg(-1). min(-1), and B: 100% enteral, total glucose intake = 7.8 +/- 0.4 mg. kg(-1). min(-1)). Splanchnic and whole-body glucose kinetics were measured by use of dual-tracer techniques. RESULTS: During both feeding periods, approximately one-third of dietary glucose intake was utilized during the first pass by the splanchnic tissues. More than three-quarters of this utilized glucose was oxidized in both periods (79 +/- 36% with A and 84 +/- 45% with B). Whole-body glucose oxidation was substantial under both circumstances: 72 +/- 5% and 77% +/- 6% of the glucose flux was oxidized during partial (A) and full (B) enteral feeding, respectively. CONCLUSIONS: Approximately one-third of dietary glucose is utilized during the first pass by the splanchnic tissues, irrespective of the dietary intake. Most of the utilized glucose is used for energy generation.

Adaptation, Physiological↗
PubMed2004

Diclofenac and metabolite pharmacokinetics in children.

BACKGROUND: Data concerning metabolism of diclofenac in children are limited to intravenous and enteric coated oral formulations. There are no data examining diclofenac or its hydroxyl metabolite pharmacokinetics after rectal administration in children. METHODS: Infants (n = 26) undergoing tonsillectomy were given diclofenac 2 mg.kg(-1) followed by 1 mg.kg(-1) 8 h as suppository formulation for postoperative analgesia. Serum was assayed for diclofenac, 4'-hydroxydiclofenac and 5'-hydroxydiclofenac concentrations during the procedure and 1, 2 and 4 h postoperatively. The formation clearances of diclofenac to hydroxyl metabolites were estimated using nonlinear mixed effects models. A single compartment, first order absorption and first order elimination model was used to describe diclofenac pharmacokinetics. Published data from 11 children given enteric-coated diclofenac tablets were used to assess relative bioavailability. RESULTS: Mean (sd) age and weight of the patients were 4.5 (1.5) years and 20.5 (4.1) kg. The formation clearance to 4'-hydroxydiclofenac (% CV) and to 5'-hydroxydiclofenac were 8.41 (8.1) and 3.41 (113) l.h(-1) respectively, standardized to a 70 kg person using allometric '1/4 power' models. Clearance by other routes contributed 33.0 (64) l.h(-1) 70 kg(-1). Elimination clearance of hydroxyl metabolites was fixed at 27.5 l.h(-1) 70 kg(-1). The volumes of distribution of parent diclofenac and its hydroxyl metabolite were 22.8 (19.0) and 45.3 (l.70) kg(-1). The suppository formulation had an absorption half-life of 0.613 (33.2) h with a lag time of 0.188 (24.9) h. Interoccasion variability of formation clearance to 4'-hydroxydiclofenac, diclofenac volume of distribution, absorption half-time and lag time for the suppository was 36%, 55%, 14% and 119%, respectively. The relative bioavailability of the suppository compared with an enteric-coated tablet was 1.26. CONCLUSION: The formation clearance of the active metabolite 4'-hydroxydiclofenac contributed 19% of total clearance (44.82 l.h(-1) 70 kg(-1)). The rectum is a suitable route for administration of diclofenac in children 2-8 year of age and was associated with a higher relative bioavailabilty than enteric-coated tablets and an earlier maximum concentration (50 vs. 108 min). This pharmacokinetic profile renders diclofenac suppository a suitable formulation for short duration surgery.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Strategy for management of newborns with cervical teratoma.

BACKGROUND: Cervical teratomas are extremely rare tumors with high perinatal mortality and morbidity rates. OBJECTIVE: To compare our experience and outcome in newborns with cervical teratoma with similar reports from the literature, in order to propose a structured approach. METHODS: A retrospective review of seven patients treated between 1986 and 2000 was performed. The results of these seven patients were compared with and added to a series of 44 well-documented patients retrieved from the literature. RESULTS: In four of the seven patients, the diagnosis was not suspected antenatally. Three of the patients survived, one died. In the other three, the diagnosis was made antenatally. Two were born using the ex-utero intrapartum treatment (EXIT) procedure, one by planned cesarean section. Only one of these three survived. Mortality in the total series of 51 patients was 33% overall, and 46% in the group in which the diagnosis had been made antenatally. Peri- and post-operative complications were reported in 27%. Although larger tumors caused polyhydramnios more frequently than smaller tumors, and were associated with more severe respiratory distress, the relationship between tumor volume at birth and final outcome could not be established. This makes difficult the identification of fetuses with a disastrous prognosis. CONCLUSION: Although mostly benign, cervical teratomas are still associated with high mortality rates. Timely antenatal diagnosis is indispensable in reducing morbidity and mortality caused by upper airway obstruction. A structured approach to the management of cervical teratoma is proposed.

Belgium↗
PubMed2003

Routine morphine infusion in preterm newborns who received ventilatory support: a randomized controlled trial.

CONTEXT: Newborns admitted to neonatal intensive care units (NICUs) undergo a variety of painful procedures and stressful events. Because the effect of continuous morphine infusion in preterm neonates has not been investigated systematically, there is confusion regarding whether morphine should be used routinely in this setting. OBJECTIVE: To evaluate the effects of continuous intravenous morphine infusion on pain responses, incidence of intraventricular hemorrhage (IVH), and poor neurologic outcome (severe IVH, periventricular leukomalacia, or death). DESIGN, SETTING, AND PATIENTS: A randomized, double-blind, placebo-controlled trial conducted between December 2000 and October 2002 in 2 level III NICUs in the Netherlands of 150 newborns who had received ventilatory support (inclusion criteria: postnatal age younger than 3 days and ventilation for less than 8 hours; exclusion criteria: severe asphyxia, severe IVH, major congenital malformations, and administration of neuromuscular blockers). INTERVENTIONS: Intravenous morphine (100 microg/kg and 10 microg/kg per hour) or placebo infusion was given for 7 days (or less because of clinical necessity in several cases). MAIN OUTCOME MEASURES: The analgesic effect of morphine, as assessed using validated scales; the effect of morphine on the incidence of IVH; and poor neurologic outcome. RESULTS: The analgesic effect did not differ between the morphine and placebo groups, judging from the following median (interquartile range) pain scores: Premature Infant Pain Profile, 10.1 (8.2-11.6) vs 10.0 (8.2-12.0) (P =.94); Neonatal Infant Pain Scale, 4.8 (3.7-6.0) vs 4.8 (3.2-6.0) (P =.58); and visual analog scale, 2.8 (2.0-3.9) vs 2.6 (1.8-4.3) (P =.14), respectively. Routine morphine infusion decreased the incidence of IVH (23% vs 40%, P =.04) but did not influence poor neurologic outcome (10% vs 16%, P =.66). In addition, analyses were adjusted for the use of additional open-label morphine (27% of morphine group vs 40% of placebo group, P =.10). CONCLUSIONS: Lack of a measurable analgesic effect and absence of a beneficial effect on poor neurologic outcome do not support the routine use of morphine infusions as a standard of care in preterm newborns who have received ventilatory support. Follow-up is needed to evaluate the long-term effects of morphine infusions on the neurobehavioral outcomes of prematurity.

Analgesics, Opioid↗
PubMed2003

Validation of the direct nasopharyngeal sampling method for collection of expired air in preterm neonates.

In clinical studies, the oxidation of 13C-labeled substrates to 13CO2 and the measurement of the appearance of excess 13CO2 in expiratory air has progressed to an increasingly common method as it is noninvasive and lacks the radiation exposure associated with the use of 14C. The collection of respiratory CO2 currently used occurs via trapping of CO2 in sodium hydroxide (trapping method), sometimes in conjunction with indirect calorimetry. The aim of the present study was to determine the accuracy of our direct nasopharyngeal sampling method for the collection of breath samples in preterm infants compared with the currently used trapping method. We present a method that simplifies the collection of breath samples in preterm infants. Seven preterm infants with a gestational age of 26-29 wk were studied on different postnatal days (range, 8-52 d) while receiving full enteral feeding. A primed constant 3-h intragastric infusion of [13C]bicarbonate was given, and breath samples were collected by means of direct nasopharyngeal sampling and by a sodium hydroxide trap simultaneously. Breath CO2 isotopic enrichments rose rapidly to reach a plateau by 120 min with <5% variation of plateau in both methods. 13CO2 breath isotopic enrichments obtained by the direct nasopharyngeal sampling method correlated highly (r2 = 0.933; p < 0.0001) with the trapping method. The Bland-Altman analysis showed no significant variability between the two methods and demonstrated that the 95% confidence interval is within +/- 4.68 delta per thousand. These findings validate the simple method of direct nasopharyngeal sampling of expired air in neonates.

Bicarbonates↗
PubMed2003

Pulmonary surfactant protein A, B, and C mRNA and protein expression in the nitrofen-induced congenital diaphragmatic hernia rat model.

Neonates with congenital diaphragmatic hernia (CDH) suffer from a diaphragmatic defect, lung hypoplasia, and pulmonary hypertension, with poor lung function forming the major clinical challenge. Despite prenatal diagnosis and advanced postnatal treatment strategies, the mortality rate of CDH is still high. CDH has been subject of extensive research over the past decades, but its etiology remains unknown. A major problem with CDH is the failure to predict the individual response to treatment modalities like high-frequency ventilation, inhaled nitric oxide, and extracorporeal membrane oxygenation. In this study, we tested the possibility that CDH lungs are surfactant protein deficient, which could explain the respiratory failure and difficulties in treating CDH infants. We investigated this hypothesis in the nitrofen-induced CDH rat model and assessed the cellular concentrations of surfactant protein (SP)-A, -B, and -C mRNA with a quantitative radioactive in situ hybridization technique. No differences were observed between control and CDH lungs for SP mRNA expression patterns. The cellular concentration (mean OD) of SP-A and SP-B mRNA was similar at all stages whereas the mean OD of SP-C mRNA and the volume fraction of cells (% Area) expressing SP mRNA was higher in CDH lungs at term. Immunohistochemical analysis revealed no differences between control and CDH lungs for SP protein expression. No differences in the mean OD or % Area for the SP mRNAs were found between the ipsi- and contralateral side of CDH lungs. We conclude that there is no primary deficiency of surfactant proteins in the nitrofen-induced CDH rat model.

Animals↗
PubMed2003

Postoperative pain in the neonate: age-related differences in morphine requirements and metabolism.

OBJECTIVE: To investigate age-related differences in morphine requirements and metabolism in full-term neonates. DESIGN AND SETTING: Randomized double-blind study in the pediatric surgical intensive care unit. PATIENTS: Sixty-eight neonates (52 aged under 7 days, 16 aged 7 day or older) following major surgery. INTERVENTIONS: After surgery patients were randomly assigned to continuous morphine (10 micro g/kg per hour) or intermittent morphine (30 micro g/kg per 3 hours). Additional morphine was administered on guidance of pain scores. MEASUREMENTS AND RESULTS: Pain was measured by the Comfort behavioral scale and visual analogue scale. Morphine and morphine-6-glucuronide (M6G) plasma concentrations were determined before and 0, 6, 12, and 24 h after surgery. The younger neonates differed significantly from the older neonates in morphine requirement (median 10 vs. 10.8 micro g/kg per hour), morphine plasma concentration [23.0 vs. 15.3 ng/ml), and M6G/morphine ratio (0.6 vs. 1.5). Pain scores did not differ between age groups or morphine treatment groups. Neonates who were mechanically ventilated longer than 24 h had significantly higher morphine plasma concentrations than the spontaneously breathing neonates 12 and 24 h after surgery (29.1 vs. 13.1 ng/ml and 26.9 vs. 12.0 ng/ml, respectively). Morphine plasma concentrations were not correlated with analgesia or respiratory depression. Five neonates (intermittent morphine) showed respiratory insufficiency; however, the difference between the groups was not significant. CONCLUSIONS: Neonates aged 7 days or younger require significantly less morphine postoperatively than older neonates. The two morphine regimens (continuous, intermittent) were equally effective and safe. Mechanical ventilation decreases morphine metabolism and clearance.

Age Factors↗
PubMed2003

Characterization of rat iodothyronine sulfotransferases.

Sulfation appears to be an important pathway for the reversible inactivation of thyroid hormone during fetal development. The rat is an often used animal model to study the regulation of fetal thyroid hormone status. The present study was done to determine which sulfotransferases (SULTs) are important for iodothyronine sulfation in the rat, using radioactive T4, T3, rT3, and 3,3'-T2 as substrates, 3'-phosphoadenosine-5'-phosphosulfate (PAPS) as cofactor, and rat liver, kidney and brain cytosol, and recombinant rat SULT1A1, -1B1, -1C1, -1E1, -2A1, -2A2, and -2A3 as enzymes. Recombinant rat SULT1A1, -1E1, -2A1, -2A2, and -2A3 failed to catalyze iodothyronine sulfation. For all tissue SULTs and for rSULT1B1 and rSULT1C1, 3,3'-T2 was by far the preferred substrate. Apparent Km values for 3,3'-T2 amounted to 1.9 microM in male liver, 4.4 microM in female liver, 0.76 microM in male kidney, 0.23 microM in male brain, 7.7 microM for SULT1B1, and 0.62 microM for SULT1C1, whereas apparent Km values for PAPS showed less variation (2.0-6.9 microM). Sulfation of 3,3'-T2 was inhibited dose dependently by other iodothyronines, with similar structure-activity relationships for most enzymes except for the SULT activity in rat brain. The apparent Km values of 3,3'-T2 in liver cytosol were between those determined for SULT1B1 and -1C1, supporting the importance of these enzymes for the sulfation of iodothyronines in rat liver, with a greater contribution of SULT1C1 in male than in female rat liver. The results further suggest that rSULT1C1 also contributes to iodothyronine sulfation in rat kidney, whereas other, yet-unidentified forms appear more important for the sulfation of thyroid hormone in rat brain.

Animals↗
PubMed2003

Paracetamol and metabolite pharmacokinetics in infants.

BACKGROUND: Data concerning metabolism of paracetamol in infants are scant. Previous studies have examined urinary metabolite recovery rates after a single dose of paracetamol in either neonates (<6 weeks) or children (3-9 years). There are no studies investigating infants. METHODS: Infants ( n=47) undergoing major craniofacial surgery were given paracetamol 19-45 mg/kg 6-, 8-, or 12-hourly as either elixir or suppository formulation for postoperative analgesia, after a loading dose of 33-59 mg/kg rectally during the operation. Serum was assayed for paracetamol concentration in 40 of these infants at 5, 8, 11, 14, 17 and 20 h postoperatively. Urine samples were collected every 3 h for 24 h in 15 of these infants. The clearances of paracetamol to glucuronide and sulphate metabolites as well as the urinary clearance of unmetabolised paracetamol were estimated using non-linear, mixed-effects models. RESULTS: Mean (+/-SD) age and weight of the patients were 11.8+/-2.5 months and 9.1+/-1.9 kg. Clearances of paracetamol to paracetamol-glucuronide (%CV) and to paracetamol-sulphate were 6.6 (11.5) l/h and 7.5 (11.5) l/h respectively, standardised to a 70-kg person using allometric "1/4 power" models. Glucuronide formation clearance, but not sulphate formation, was related to age and increased with age from a predicted value in a neonate of 2.73 l/h/70 kg to a mature value of 6.6 l/h/70 kg with a maturation half-life of 8.09 months. Urine clearance of paracetamol-glucuronide, paracetamol-sulphate and unchanged paracetamol (%CV) were, respectively, 2.65, 3.03 and 0.55 (28) l/h/70 kg. The urine clearance of unchanged paracetamol and metabolites was related to urine volume flow rate. Clearance attributable to pathways other than these measured in urine was not identifiable. The glucuronide/sulphate formation clearance ratio was 0.69 at 12 months of age. Sulphate metabolism contributed 50% towards paracetamol clearance. CONCLUSION: Glucuronide formation clearance increases with age in the infant age range but sulphate formation does not. Renal clearance of paracetamol and its metabolites increases with urine flow rate. This and other studies show that paracetamol metabolism to glucuronide appears to be similar in infants and children, but in adults is increased in comparison with children. Oxidative pathways were undetectable in this infant study and may explain, in part, the reduced incidence of hepatotoxicity in infants.

Acetaminophen↗
PubMed2003

Systematic evaluation of pain in neonates: effect on the number of intravenous analgesics prescribed.

OBJECTIVE: To document the effect of systematic evaluation of pain in neonates on prescription of intravenous analgesics in a level-III neonatal intensive care unit (NICU) as a marker of increased awareness of treating and preventing pain. METHODS: Retrospective analysis of the number of yearly prescribed vials of intravenous analgesics in a level-III NICU during a period before (1996-1999) and after (2000 to August 2002) introduction of a multidimensional pain scale. Correction was carried out by multiple regression analysis for clinical co-variables (admissions, days on parenteral nutrition, days on respiratory support, surgical procedures), which also might explain changes in prescription of analgesics. Postoperative length (hours) of administration of analgesics was calculated in a group of infants (1996-2001) who all received cryotherapy for threshold retinopathy of prematurity (ROP) before (1996-1999) and since (2000-2001) introduction of pain evaluation. RESULTS: The number of yearly prescribed vials increased from 3140+/-619 (mean+/-SD) to 5915+/-675 ( P<0.005). There is also a significant increase in the number of surgical interventions ( P<0.05) but not in days on respiratory support, days on parenteral nutrition or in number of admissions. After correction for the number of surgical procedures, the increase in prescribed vials remained significant ( P<0.05). In infants who received cryotherapy, a significant increase in length of postoperative analgesia (65-107 h, P<0.01) was documented. Even after correction for the increased postoperative length of ventilation, duration of postoperative analgesia remained significantly ( P<0.05) longer. CONCLUSIONS: Systematic evaluation of pain increased awareness of treating and preventing pain in neonates, even after correction for clinical co-variables. This increase was not associated with an increase in potential side-effects (length of respiratory support, length of parenteral nutrition).

Acetaminophen↗
PubMed2003

Do we still hurt newborn babies? A prospective study of procedural pain and analgesia in neonates.

BACKGROUND: Despite an increasing awareness regarding pain management in neonates and the availability of published guidelines for the treatment of procedural pain, preterm neonates experience pain leading to short- and long-term detrimental effects. OBJECTIVE: To assess the frequency of use of analgesics in invasive procedures in neonates and the associated pain burden in this population. METHODS: For 151 neonates, we prospectively recorded all painful procedures, including the number of attempts required, and analgesic therapy used during the first 14 days of neonatal intensive care unit admission. These data were linked to estimates of the pain of each procedure, obtained from the opinions of experienced clinicians. RESULTS: On average, each neonate was subjected to a mean +/- SD of 14 +/- 4 procedures per day. The highest exposure to painful procedures occurred during the first day of admission, and most procedures (63.6%) consisted of suctioning. Many procedures (26 of 31 listed on a questionnaire) were estimated to be painful (pain scores >4 on a 10-point scale). Preemptive analgesic therapy was provided to fewer than 35% of neonates per study day, while 39.7% of the neonates did not receive any analgesic therapy in the neonatal intensive care unit. CONCLUSIONS: Clinicians estimated that most neonatal intensive care unit procedures are painful, but only a third of the neonates received appropriate analgesic therapy. Despite the accumulating evidence that neonatal procedural pain is harmful, analgesic treatment for painful procedures is limited. Systematic approaches are required to reduce the occurrence of pain and to improve the analgesic treatment of repetitive pain in neonates.

Analgesics↗
PubMed2003

Association of congenital diaphragmatic hernia with limb-reduction defects.

BACKGROUND: The pathogenesis of congenital diaphragmatic hernia (CDH), a severe birth defect, is not well understood; however, both developmental genes and environmental factors have been suggested to be involved. CDH is frequently associated with malformations of other structures, such as limbs, whose embryogenesis is better understood. An examination of the co-occurrence of developmental defects may provide clues as to the origin and timing of the insult to the diaphragm and limbs. Our focus was on CDH-associated limb-reduction defects (LRDs). METHODS: For this descriptive study, we reviewed the medical records of infants with a posterolateral (Bochdalek) CDH and an associated LRD among 146 patients from the Sophia Children's Hospital, and among 810 infants and 36 stillbirths from the California Birth Defects Monitoring Program (CBDMP). RESULTS: In the hospital group, 14 patients (10%) had an associated limb defect, of which about one-third were LRDs (of these, most were of a nonsevere type, such as hypoplasia of fingers). In the registry group, a limb defect was found in 162 cases (18.5%), 18 of which were mostly severe LRD (usually of the upper extremities). Additional congenital anomalies were observed in all CDH-LRD cases in both groups. CONCLUSIONS: In the registry group, 77.8% of LRDs were either bilateral or ipsilateral, and were mostly preaxial, suggesting an early embryological insult affecting both precursor anlages. These results, from large numbers of cases, support the notion of a developmental association between CDH and LRD, as has been observed in several knockout mice. Future analyses of candidate genes from patients with CDH and LRD may elucidate this developmental association in humans.

Female↗
PubMed2003

Down-regulation of sonic hedgehog expression in pulmonary hypoplasia is associated with congenital diaphragmatic hernia.

The pathogenesis of pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) is unknown. The sonic hedgehog (Shh) cascade is crucial for the patterning of the early respiratory system in mice. To establish whether Shh plays a role in the pathogenesis of lung hypoplasia in CDH, we investigated the gestation-specific expression of Shh in normal rat and human lungs using in situ hybridization and immunohistochemistry. The expression pattern was compared with that of age-matched samples of hypoplastic lungs associated with CDH in humans and in the 2,4-dichlorophenyl-p-nitrophenylether (nitrofen) rat model. Our results showed that in normal controls the expression of Shh increased with advancing gestation, peaked in the late pseudoglandular stage, and declined thereafter. The expression of Shh is initially down-regulated in pulmonary hypoplasia associated with CDH and peaks instead during the late canalicular stage. These data indicate that maximal expression of Shh occurs when respiratory bronchioles develop and thinning of the interstitium takes place, suggesting that Shh may play a role in these processes. Furthermore, we observed that Shh inhibited fetal lung fibroblast proliferation in vitro. Therefore, it is tempting to speculate that alterations in Shh expression may affect these developmental processes, thereby contributing to the pulmonary abnormality in CDH.

Animals↗
PubMed2003

Measuring pain in children with cognitive impairment: pain response to surgical procedures.

This study investigated post-surgical pain in children with profound cognitive impairment (PCI), searching for a core set of cues these children use to express their pain. Fifty-two children were observed while they were admitted to the Sophia Children's Hospital for surgery, twice before and five times after surgery. All observations were scored with the item pool consisting of 134 possible pain indicators, using a five-point scale ranging from 0 (never shown) to 4 (always shown). Second, we used the visual analogue scale (VAS) to give a general impression of the severity of the children's pain during the episodes they were observed. Several analyses provided evidence that 23 observable behaviors are sensitive to post-surgical pain in children with PCI, regardless of the pain intensity of the surgical procedures they underwent. The finding that all indicators, except for one, were scored significantly higher on episodes with VAS ratings >or=4, indicates the sensitivity of these indicators concerning absence versus presence of clinically meaningful levels of pain. This study reveals the potential clinical utility of a core set of indicators which can be used to assess post-surgical pain in children with PCI.

Adolescent↗
PubMed2003

Surfactant phosphatidylcholine pool size in human neonates with congenital diaphragmatic hernia requiring ECMO.

OBJECTIVE: We measured surfactant phosphatidylcholine (PC) pool size and half-life in human congenital diaphragmatic hernia (CDH) patients who required extracorporeal membrane oxygenation (ECMO). Study design Surfactant PC pool size and half-life were measured by endotracheal administration of deuterium-labeled dipalmitoylphosphatidylcholine in 8 neonates with CDH on ECMO (CDH-ECMO), in 7 neonates with meconium aspiration syndrome on ECMO (MAS-ECMO), and in 6 ventilated infants (NON-ECMO). RESULTS: Lung PC pool size in the CDH-ECMO group was 73 +/- 17 mg/kg (mean +/- SEM), which was not significantly different from the MAS-ECMO (50 +/- 18 mg/kg) and the NON-ECMO group (69 +/- 38 mg/kg). Surfactant PC concentration in tracheal aspirates was not different between groups (~6 mg/mL). However, the percentage of palmitic acid in surfactant PC was significantly lower in the MAS-ECMO (56.3%) and the NON-ECMO (55.8%) group compared with the CDH-ECMO (67.6%) group. Surfactant PC half-life (~24 hours) was not different between the groups. A correlation was found between the surfactant PC half-life and the duration of ECMO. CONCLUSIONS: These data show no decreased surfactant PC pool size in high risk CDH patients who require ECMO. A shorter half-life of surfactant PC, indicating a faster turnover, may result in a faster improvement of the pulmonary condition during ECMO.

1,2-Dipalmitoylphosphatidylcholine↗