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1.
Sci Rep ; 11(1): 13777, 2021 07 02.
Article in English | MEDLINE | ID: mdl-34215818

ABSTRACT

Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are two of the most common emergencies of the gastrointestinal tract in preterm infants with very low birth weight (VLBW, birth weight < 1500 g). Identification of risk factors among these children is crucial for earlier diagnosis and prompt intervention. In this study, we investigated a relationship between ABO blood groups and the risk for surgical NEC/FIP. We genotyped the ABO locus (rs8176746 and rs8176719) in VLBW infants enrolled in a prospective, population-based cohort study of the German Neonatal Network (GNN). Of the 10,257 VLBW infants, 441 (4.3%) had surgical NEC/FIP. In univariate analyses, the blood group AB was more prevalent in VLBW infants with surgical NEC/FIP compared to non-AB blood groups (OR 1.51, 95% CI 1.07-2.13, p = 0.017; absolute risk difference 2.01%, 95% CI 0.06-3.96%). The association between blood group AB and surgical NEC/FIP was observed in a multivariable logistic regression model (OR of 1.58, 95% CI 1.10-2.26, p = 0.013) as well. In summary, our study suggests that the risk of surgical NEC and FIP is higher in patients with blood group AB and lower in those having non-AB blood groups.


Subject(s)
ABO Blood-Group System/blood , Enterocolitis, Necrotizing/epidemiology , Infant, Newborn, Diseases/epidemiology , Infant, Premature, Diseases/epidemiology , Intestinal Perforation/epidemiology , Child, Preschool , Enterocolitis, Necrotizing/blood , Enterocolitis, Necrotizing/pathology , Enterocolitis, Necrotizing/surgery , Female , Fetal Diseases/blood , Fetal Diseases/pathology , Fetal Diseases/surgery , Gestational Age , Humans , Infant , Infant, Newborn , Infant, Newborn, Diseases/blood , Infant, Newborn, Diseases/pathology , Infant, Newborn, Diseases/surgery , Infant, Premature/blood , Infant, Premature, Diseases/pathology , Infant, Premature, Diseases/surgery , Infant, Very Low Birth Weight , Intestinal Perforation/blood , Intestinal Perforation/pathology , Intestinal Perforation/surgery , Male , Risk Factors
2.
Seizure ; 80: 212-220, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32645639

ABSTRACT

Epileptic encephalopathies are conditions in which the abundant epileptiform activity itself interferes with development, resulting in cognitive slowing and often regression, psychiatric and behavioral disturbances. Nonconvulsive status epilepticus has been defined as ongoing or nonrecovering nonconvulsive seizures. It has been challenging to differentiate clinical and electroencephalographic patterns in epileptic encephalopathies from those attributed to nonconvulsive status epilepticus, since several different epileptic encephalopathies may show continuous or subcontinuous epileptiform activity. Especially for patients with known epileptic encephalopathy, the new proposal for diagnosis of nonconvulsive status epilepticus suggests an increase in prominence or frequency of specific electroencephalographic features as compared to baseline correlated to clinical and EEG responsiveness to intravenous anti-seizure drugs. This clinical change may be unclear, particularly in patients with pre-existent cognitive or behavioral impairments. This review intends to organize previously published data, with available information in the literature on some of those specific epileptic syndromes and diseases, focusing on two main questions: i. When should specialists suspect of nonconvulsive status epilepticus in epileptic encephalopathies? ii. Could epileptic encephalopathies themselves be nonconvulsive status epilepticus presentations? Lastly, the rationale for definition and treatment in many of the epileptic encephalopathies is the effect of ongoing frequent epileptiform activity on development and cognition, and this will require monitoring with serial clinical, neurophysiological, functional neuroimaging, and neuropsychological assessments. Whether there would be an association or causality between epileptic encephalopathies and nonconvulsive status epilepticus is a key question demanding further research.


Subject(s)
Epilepsy, Generalized , Status Epilepticus , Electroencephalography , Humans , Neuropsychological Tests , Seizures , Status Epilepticus/complications , Status Epilepticus/diagnosis
3.
Gesundheitswesen ; 80(2): 122-128, 2018 Feb.
Article in German | MEDLINE | ID: mdl-26990609

ABSTRACT

BACKGROUND: Malformations are the most common cause of death in infancy. Numerous studies indicate an increased prevalence of malformations in neonates in recent years in some countries around the world. This study analyzed local and national trends of the prevalences of gastroschisis, omphalocele, spina bifida and orofacial clefts during 2000 till 2010 in Leipzig, Saxony, Saxony-Anhalt and Germany. METHODS: The prevalence of neonatal malformations was studied retrospectively from January 2000 till December 2010 using 4 sources from Leipzig, Saxony, Saxony-Anhalt and Germany. RESULTS: Between 2000 and 2010, the prevalence in Germany and in Saxony, respectively was 1.97/2.12 (gastroschisis), 1.63/1.48 (omphalocele), 5.80/8.11 (orofacial clefts) and 2.92/2.50 (spina bifida) of 10 000 live births. In Saxony, a small increase in prevalence was detected (OR/year: 1.01-1.09). In Germany, the prevalence of malformations also increased significantly (OR/year: 1.01-1.04) with the exception of the prevalence of spina bifida which seemed to decline (OR/year 0.986 (0.97-1.0), p-adjust=0.04). CONCLUSION: Whether or not there has been an actual increase in the prevalence of neonatal malformations in Germany over the years or the apparent increase is just due to bias, coding errors, multiple reporting and/or false registration and codification remains unclear. Importantly, in Germany, since prevalence of malformations is monitored prospectively only in Saxony-Anhalt and Rhineland-Palatinate, only in these states is it possible to recognize recent changes. For early identification of changes in prevalence and timely implementation of preventive measures, a nationwide register or additional regional registers are deemed necessary.


Subject(s)
Cleft Lip , Cleft Palate , Gastroschisis , Hernia, Umbilical , Spinal Dysraphism , Cleft Lip/epidemiology , Cleft Palate/epidemiology , Gastroschisis/epidemiology , Germany/epidemiology , Hernia, Umbilical/epidemiology , Humans , Infant, Newborn , Prevalence , Retrospective Studies , Spinal Dysraphism/epidemiology
5.
Laryngorhinootologie ; 95(10): 674-683, 2016 Oct.
Article in German | MEDLINE | ID: mdl-27764854

ABSTRACT

Objective: The diagnosis of cancer in pregnancy is rare, but might become more relevant even for head and neck cancer patients due to a shift of age of primipara towards the last third of reproductive years. Unsureness exists about the risk and benefit of diagnostic and therapeutic cancer modalities for the unborn and established recommendations are still missing. But, according to recent data, even multimodal therapeutic approaches (e. g. surgery, radiation, chemotherapy) seem possible in face of pregnancy and should be traded against the risk of prematurity. Material and Methods: Our findings are discussed on the basis of a case report of a pregnant woman with advanced carcinoma of the outer ear canal and therapy options are formulated. Results: Sufficient performed diagnostic modalities do not reach imperilling uterus dosages. A growing number of case reports und studies did not detect any developmental disadvantage of children of prenatal exposed mothers by radiation or chemotherapy, whereas long-term impairments of premature infants are proven. Conclusion: In cancer in pregnancy, an immediate start of well-established therapy modalities like surgery and/or cisplatin-based chemoradiation seems to be possible without unjustifiable risks for the unborn.


Subject(s)
Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/therapy , Otorhinolaryngologic Neoplasms/diagnosis , Otorhinolaryngologic Neoplasms/therapy , Pregnancy Complications, Neoplastic/diagnosis , Pregnancy Complications, Neoplastic/therapy , Adult , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy, Adjuvant/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Combined Modality Therapy/adverse effects , Diagnosis, Differential , Female , Gestational Age , Humans , Infant, Newborn , Magnetic Resonance Imaging , Neoplasm Staging , Otorhinolaryngologic Neoplasms/pathology , Petrous Bone/pathology , Positron Emission Tomography Computed Tomography , Pregnancy , Pregnancy Complications, Neoplastic/pathology , Radiotherapy Dosage , Risk , Tomography, X-Ray Computed
6.
Early Hum Dev ; 91(12): 677-81, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26513628

ABSTRACT

AIMS: The study investigated the association between clinical symptoms and late-onset sepsis (LOS) in preterm infants with the aim of identifying a non-invasive tool for the early detection of LOS. METHODS: This was a prospective study of 83 episodes of suspected LOS in 67 preterm infants. At the time LOS was suspected, we recorded a standardized set of clinical symptoms. A diagnosis of "clinical LOS" (Clin-LOS), "culture-proven LOS" (Prov-LOS) or "LOS not present" (No-LOS) was made on the basis of C-reactive protein (CrP) and blood culture results where Clin-LOS was defined as CrP>10mg/l, Prov-LOS was defined as CrP>10mg/l AND positive blood cultures, or it was established that there was no sepsis present (No-LOS). We examined univariable associations between clinical signs and LOS using odds ratio (OR) analysis and then adjusted the odds ratio (adOR) through binary regression analysis. RESULTS: Clin-LOS was diagnosed in 20/83 episodes, 19 cases were found to have Prov-LOS. Clinical signs which had a significant association with Clin-LOS were capillary refill time >2s (OR 2.9) and decreased responsiveness (OR 5.2), whereas there was a negative association between gastric residuals and LOS (OR 0.35). However, the most marked association was found for a greater central-peripheral temperature difference (cpTD) >2°C (OR 9). In Prov-LOS an increased heart rate (OR 3.1), prolonged capillary refill time (OR 3.3) and again an increased cpTD (OR 16) had a significant association with LOS, whereas gastric residuals were negatively associated (OR 0.29). Regression analysis showed that cpTD was the most striking clinical sign associated with both Clin- (adOR 6.3) and Prov-LOS (adOR 10.5). CONCLUSIONS: Prolonged capillary refill time and - more impressive - elevated cpTD were the most useful clinical symptoms for detection of LOS in preterm infants. We especially suggest using cpTD as a predictor of LOS. It is a cheap, non-invasive and readily available tool for daily routines.


Subject(s)
Body Temperature/physiology , Infant, Premature, Diseases/diagnosis , Sepsis/diagnosis , Early Diagnosis , Female , Humans , Infant , Infant, Newborn , Infant, Premature , Male , Prospective Studies
7.
Z Geburtshilfe Neonatol ; 219(6): 259-65, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26151478

ABSTRACT

The rates of delivery by Cesarean section (CS) have been trending upwards in recent decades, perhaps leading to higher rates of dysfunction in respiratory adaptation in newborns. We present epidemiological data for pulmonary adaptation by mode of delivery for healthy late preterm and term infants born at a regional tertiary care center. The overall CS rate was 22% with the largest proportion of these in late preterms (39%). This drops to 30% in infants born after 37 weeks gestation and to 11% for those born after 40 weeks. Infants needing respiratory support decreased significantly as gestational age increased: 88% at 34 weeks, 67% at 35 weeks, 28% at 36 weeks, 17% at 37 weeks and 8% at 40 weeks. The risk of respiratory morbidity following CS as compared to vaginal delivery (VD) was substantially higher. 50% of infants born by CS needed respiratory support compared to only 12% following VD. 82% of all late preterm infants born by CS developed respiratory morbidity compared to 36% following VD. Comparable data for infants born after 37 and 40 weeks gestation were 33% compared to 9% and 26% compared to 6% respectively. Late preterm infants born after 36 weeks gestation showed the most marked difference by mode of birth with 66% needing respiratory support following CS as compared to only 9% following VD. Our data could be useful in counselling parents about risk associated with delivery by Cesarean section. A critical view should be taken of increasing CS rates worldwide because of a clear correlation in increased morbidity in infants, especially late preterm infants.


Subject(s)
Cesarean Section/statistics & numerical data , Natural Childbirth/statistics & numerical data , Postoperative Complications/epidemiology , Premature Birth/epidemiology , Respiratory Distress Syndrome, Newborn/epidemiology , Causality , Comorbidity , Female , Germany/epidemiology , Humans , Incidence , Infant, Newborn , Male , Risk Factors , Treatment Outcome
9.
J Perinatol ; 34(3): 244-6, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24573211

ABSTRACT

The use of dexamethasone in preterm infants developing bronchopulmonary dysplasia has been proven to be effective. Hypertrophic cardiomyopathy is a frequently reported, although transient, side effect of high-dose dexamethasone administration. The recent introduction of very low dexamethasone dose, called 'Minidex', promised equal effectiveness compared to high-dose dexamethasone without relevant side effects. Our study presents two patients developing hypertrophic cardiomyopathy with intraventricular cardiac obstruction after administration of 'Minidex'. Marked cardiac side effects may occur even during very-low-dose dexamethasone treatment in preterm neonates. Betablocker and discontinuation of dexamethasone seem to allow spontaneous reversal of myocardial hypertrophy and obstruction. After all, systematic surveys of the incidence of cardiac complications in a larger population of preterm infants treated with very low doses of dexamethasone are needed.


Subject(s)
Cardiomegaly/chemically induced , Dexamethasone/adverse effects , Infant, Premature, Diseases/chemically induced , Ventricular Outflow Obstruction/chemically induced , Bronchopulmonary Dysplasia/prevention & control , Dexamethasone/administration & dosage , Echocardiography , Humans , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/diagnostic imaging , Ventricular Outflow Obstruction/diagnostic imaging
10.
J Perinatol ; 33(4): 282-7, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22935773

ABSTRACT

OBJECTIVE: The study investigated the ability of near-infrared spectroscopy (NIRS) to detect subgroups of preterm infants who benefit most from red blood cell (RBC) transfusion in regard to cerebral/renal tissue oxygenation (i) and the number of general oxygen desaturation below 80% (SaO(2) <80%) (ii). STUDY DESIGN: Cerebral regional (crSO(2)) and peripheral regional (prSO(2)) NIRS parameters were recorded before, during, immediately after and 24 h after transfusion in 76 infants. Simultaneously, SaO(2) <80% were recorded by pulse oximetry. To answer the basic question of the study, all preterm infants were divided into two subgroups according to their pretransfusion crSO(2) values (<55% and ≥55%). This cutoff was determined by a k-means clustering analysis. RESULT: crSO(2) and prSO(2) increased significantly in the whole study population. A stronger increase (P<0.0005) of both was found in the subgroup with pretransfusion crSO(2) values <55%. Regarding the whole population, a significant decrease (P<0.05) of episodes with SaO(2) <80% was observed. The subgroup with crSO(2) baselines <55% had significant (P<0.05) more episodes with SaO(2) <80% before transfusion. During and after transfusion, the frequency of episodes with SaO(2) <80% decreased more in this group compared with the group with crSO(2) baselines ≥55%. CONCLUSION: NIRS measurement is a simple, non-invasive method to monitor regional tissue oxygenation and the efficacy of RBC transfusion. Infants with low initial NIRS values benefited most from blood transfusions regarding SaO(2) <80%, which may be important for their general outcome.


Subject(s)
Anemia, Neonatal , Brain/metabolism , Erythrocyte Transfusion/methods , Kidney/metabolism , Oxygen Consumption , Spectroscopy, Near-Infrared/methods , Anemia, Neonatal/metabolism , Anemia, Neonatal/therapy , Female , Gestational Age , Humans , Infant, Newborn , Infant, Premature , Male , Monitoring, Physiologic/methods , Oxygen/metabolism , Practice Guidelines as Topic , Reproducibility of Results , Treatment Outcome
12.
Br J Pharmacol ; 168(6): 1329-40, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23083067

ABSTRACT

BACKGROUND AND PURPOSE: Pharmacological enhancement of vectorial Na⁺ transport may be useful to increase alveolar fluid clearance. Herein, we investigated the influence of the benzimidazolones 1-ethyl-1,3-dihydro-2-benzimidazolone (1-EBIO), 5,6-dichloro-1-EBIO (DC-EBIO) and chlorzoxazone on vectorial epithelial Na⁺ transport. EXPERIMENTAL APPROACH: Effects on vectorial Na⁺ transport and amiloride-sensitive apical membrane Na⁺ permeability were determined by measuring short-circuit currents (I(SC)) in rat fetal distal lung epithelial (FDLE) monolayers. Furthermore, amiloride-sensitive membrane conductance and the open probability of epithelial Na⁺ channels (ENaC) were determined by patch clamp experiments using A549 cells. KEY RESULTS: I(SC) was increased by approximately 50% after addition of 1-EBIO, DC-EBIO and chlorzoxazone. With permeabilized basolateral membranes in the presence of a 145:5 apical to basolateral Na⁺ gradient, the benzimidazolones markedly increased amiloride-sensitive I(SC). 5-(N-Ethyl-N-isopropyl)amiloride-induced inhibition of I(SC) was not affected. The benzamil-sensitive I(SC) was increased in benzimidazolone-stimulated monolayers. Pretreating the apical membrane with amiloride, which inhibits ENaC, completely prevented the stimulating effects of benzimidazolones on I(SC). Furthermore, 1-EBIO (1 mM) and DC-EBIO (0.1 mM) significantly increased (threefold) the open probability of ENaC without influencing current amplitude. Whole cell measurements showed that DC-EBIO (0.1 mM) induced an amiloride-sensitive increase in membrane conductance. CONCLUSION AND IMPLICATIONS: Benzimidazolones have a stimulating effect on vectorial Na⁺ transport. The antagonist sensitivity of this effect suggests the benzimidazolones elicit this action by activating the highly selective ENaC currents. Thus, the results demonstrate a possible new strategy for directly enhancing epithelial Na⁺ transport.


Subject(s)
Benzimidazoles/pharmacology , Chlorzoxazone/pharmacology , Epithelial Sodium Channel Agonists/pharmacology , Epithelial Sodium Channels/metabolism , Pulmonary Alveoli/drug effects , Respiratory Mucosa/drug effects , Animals , Benzimidazoles/antagonists & inhibitors , Cell Line , Cell Membrane Permeability/drug effects , Cell Polarity/drug effects , Cells, Cultured , Chlorzoxazone/antagonists & inhibitors , Epithelial Sodium Channel Agonists/antagonists & inhibitors , Epithelial Sodium Channel Blockers/pharmacology , Fetus/cytology , Humans , Membrane Potentials/drug effects , Patch-Clamp Techniques , Pulmonary Alveoli/cytology , Pulmonary Alveoli/metabolism , Rats , Respiratory Mucosa/cytology , Respiratory Mucosa/metabolism , Single-Cell Analysis , Sodium/metabolism
13.
Klin Padiatr ; 224(5): 324-30, 2012 Sep.
Article in German | MEDLINE | ID: mdl-22915454

ABSTRACT

BACKGROUND: The accurately timed extubation of ventilated ELBW preterm infants is still a problem. With different data systems the attempt has been made to more accurately predict the successful extubation of these infants. However, there do not yet exist any satisfying solutions. PATIENTS/METHODS: We retrospectively analysed 66 ELBW preterm infants who were endotracheal intubated and ventilated within 24 h postnatal. Basic data, clinical and ventilation data immediately before planned extubation and in several intervals during the following 24 h, as well as outcome variables at discharge were interpreted. RESULTS: 51 patients were successfully extubated (EE-group), 15 (22.7%) failed extubation (reintubation within 48 h after extubation, EV-group). Immediately before extubation in the EE-group there was found a significantly higher inspiratory oxygen concentration (FiO2) in comparison to the EV-group (0.25 vs. 0.3; p=0.01). After the extubation attempt the inspiratory oxygen concentration stayed lower in the EE-group, whereas in the EV-group it rose remarkably (2 h after ext.: 0.26 vs. 0.4; p<0.001). Neither of the basic data showed any significant difference. The outcome analysis indicated a longer intensive care in the EV-group and a trend towards increased BPD and ROP. CONCLUSION: The study shows that for ELBW preterm infants the inspiratory oxygen concentration is especially important to predict a successful extubation. According to our data, the inspiratory oxygen demand before and immediately after extubation establishes the essential difference between successfully extubated and reintubated infants.


Subject(s)
Airway Extubation , Infant, Extremely Low Birth Weight , Oxygen/blood , Respiratory Distress Syndrome, Newborn/therapy , Ventilator Weaning , Apnea/blood , Apnea/therapy , Female , Germany , Humans , Infant, Newborn , Inhalation/physiology , Male , Predictive Value of Tests , Prognosis , Pulmonary Surfactants/administration & dosage , Respiratory Distress Syndrome, Newborn/blood , Respiratory Function Tests , Retrospective Studies , Risk Factors , Treatment Failure , Treatment Outcome
14.
Arch Dis Child Fetal Neonatal Ed ; 90(6): F466-73, 2005 Nov.
Article in English | MEDLINE | ID: mdl-15941826

ABSTRACT

OBJECTIVE: Randomised controlled trials comparing elective use of high frequency ventilation (HFV) with conventional mechanical ventilation (CMV) in preterm infants have yielded conflicting results. We hypothesised that the variability of results may be explained by differences in study design, ventilation strategies, delay in initiation of HFV, and use of permissive hypercapnia. METHODS: Randomised controlled trials comparing the elective use of HFV with any form of CMV were identified. Trials were classified according to the ventilation strategies used for HFV and CMV and oscillator device employed. For cumulative meta-analyses, trials were arranged by the following covariables: mean duration until randomisation, Paco(2) limits, publication date, and sample size. Odds ratios (OR) and 95% confidence intervals were calculated using fixed and random effects models. RESULTS: Seventeen randomised trials enrolling 3776 patients were included. Unlike previous meta-analyses, there was no significant difference in the incidence of bronchopulmonary dysplasia or death (OR 0.87, 0.75-1.00) and severe intraventricular haemorrhage grade 3-4 (1.14, 0.96-1.37). The incidence of air leaks (OR 1.23, 1.06-1.44) was significantly increased with HFV. Subgroup analyses and cumulative meta-analyses demonstrated that trial results were related to the ventilation strategies used for HFV and CMV. No influence was found for mean time to randomisation, degree of permissive hypercapnia, or sample size. CONCLUSIONS: Heterogeneity among trials of elective HFV compared to CMV in preterm infants is mainly due to differences in ventilatory strategies. Optimising CMV strategy appeared to be as effective as using HFV in improving pulmonary outcome in preterm infants.


Subject(s)
High-Frequency Ventilation/methods , Infant, Premature, Diseases/therapy , Intensive Care, Neonatal/methods , Humans , Infant, Newborn , Infant, Premature , Randomized Controlled Trials as Topic/methods , Research Design , Respiration, Artificial/methods , Treatment Outcome
16.
Crit Care Med ; 29(6): 1175-80, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11395598

ABSTRACT

OBJECTIVE: We hypothesized that partial liquid ventilation (PLV) would improve oxygenation in nonparalyzed, surfactant-deficient rabbits breathing spontaneously while supported by proportional assist ventilation (PAV). This ventilation mode compensates for low pulmonary compliance and high resistance and thereby facilitates spontaneous breathing. DESIGN: Randomized trial. SETTING: University animal research facility. SUBJECTS: Twenty-six anesthetized New Zealand white rabbits weighing 2592 +/- 237g (mean +/- sd). INTERVENTIONS: After pulmonary lavage (target Pao2 <100 mm Hg on mechanical ventilation with 6 cm H2O of positive end-expiratory pressure [PEEP] and an Fio2 of 1.0), rabbits were randomized to PAV (PEEP of 8 cm H2O) with or without PLV. PLV rabbits received 25 mL/kg of perfluorocarbon by intratracheal infusion (1 mL/kg/min). Pao2, Paco2, tidal volume, respiratory rate, minute ventilation, mean airway pressure, arterial blood pressure, heart rate, pulmonary compliance, and airway resistance were measured. Evaporated perfluorocarbon was refilled every 30 mins in PLV animals. After 5 hrs, animals were killed and lungs were removed. Lung injury was evaluated using a histologic score. MAIN RESULTS: Pao2 and compliance were significantly higher in PLV rabbits compared with controls (p <.05, analysis of variance for repeated measures). All other parameters were similar in both groups. CONCLUSIONS: PLV improved oxygenation and pulmonary compliance in spontaneously breathing, severely surfactant-depleted rabbits supported by PAV. The severity of lung injury by histology was unaffected.


Subject(s)
Liquid Ventilation , Positive-Pressure Respiration , Pulmonary Surfactants/deficiency , Respiration, Artificial/methods , Respiratory Distress Syndrome/prevention & control , Respiratory Distress Syndrome/physiopathology , Analysis of Variance , Animals , Female , Lung Compliance , Oxygen/metabolism , Pulmonary Gas Exchange , Rabbits , Respiratory Mechanics , Statistics, Nonparametric
17.
Pediatr Res ; 49(4): 572-80, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11264443

ABSTRACT

Partial liquid ventilation (PLV) has been shown to improve gas exchange in paralyzed animals and humans with lung disease. The present study tests the hypothesis that PLV improves gas exchange in spontaneously breathing animals with meconium aspiration supported by proportional assist ventilation. Twenty-five adult anesthetized intubated rabbits with experimental meconium aspiration were randomized to gas ventilation (GV) or PLV while being supported by proportional assist ventilation. Minute ventilation, tidal volume, respiratory rate, mean airway pressure, heart rate, and mean arterial and pulmonary arterial pressure were recorded continuously. Every 30 min, arterial blood gases were obtained, and lung compliance, airway resistance, work of breathing, and cardiac output were measured. Animals were sacrificed after 5 h to obtain lung histology. More PLV animals survived until the end of the study period. PaO(2) (14.5 +/- 4.5 versus 25.6 +/- 6.7 kPa; p < 0.01; GV versus PLV) and lung compliance (4.3 +/- 0.4 versus 6.1 +/- 1.2 mL.kPa(-1).kg(-1); p < 0.001) were improved during PLV, resulting in a lower work of breathing (5.3 +/- 2.8 versus 3.5 +/- 1.5 mL.kPa.kg(-1); p < 0.05) and less need for ventilatory support. Minute ventilation and respiratory rate were higher during GV versus PLV, resulting in a slightly lower PaCO(2) (3.9 +/- 0.5 versus 4.5 +/- 0.7 kPa; p < 0.05). Histologic evaluation showed more atelectasis, inflammatory changes, and hemorrhage in GV animals. Other parameters measured were similar. We conclude that PLV improves oxygenation, lung compliance, and survival and results in less lung injury in spontaneously breathing animals with meconium aspiration when supported by proportional assist ventilation.


Subject(s)
Liquid Ventilation , Meconium Aspiration Syndrome , Respiration , Animals , Female , Hemodynamics , Humans , Infant, Newborn , Lung/anatomy & histology , Pneumothorax/physiopathology , Rabbits
18.
Am J Respir Cell Mol Biol ; 24(3): 245-52, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11245623

ABSTRACT

We investigated whether adenovirus-mediated transfer of genes encoding for subunits of the Na,K-ATPase increases transepithelial Na(+) transport in rat fetal distal lung epithelial (FDLE) monolayers and renders them more resistant to hydrogen peroxide injury. FDLE cells, isolated from rat fetuses at a gestational age of 19 to 20 d (22 d = term), were seeded on filters and infected with replication-incompetent human type 5 adenoviruses containing complementary DNAs encoding for rat Na,K-ATPase alpha(1) or beta(1) subunits (ad alpha(1) and ad beta(1), respectively). Once confluent monolayers were formed, the filters were mounted in Ussing chambers and short circuit currents (I(SC)) were measured. Increased levels of alpha(1) or beta(1) subunit proteins after infection with ad alpha(1) and ad beta(1), respectively, were confirmed by Western blot analysis. Baseline I(SC) increased after transfection with 2 plaque-forming units (pfu) of ad beta(1) from 5.1 +/- 0.3 to 6.1 +/- 0.3 microA/cm(2) (mean +/- SEM; P < 0.05). Permeabilization of the apical membrane with amphotericin B caused a large increase in I(SC); the ouabain-sensitive component of the amphotericin B-elicited I(SC) (ouab(max)) was increased from 4.0 +/- 0.2 (n = 69) in controls to 4.8 +/- 0.2 (n = 15), 5.9 +/- 0.3 (n = 53), 6.9 +/- 0.4 (n = 25), 7.7 +/- 0.9 (n = 16) in monolayers infected with 1, 2, 11, and 22 pfu of ad beta(1), respectively; transfection with ad alpha(1) had no effect on any measured variables. Further, transfection with ad beta(1) in comparison to noninfected monolayers resulted in higher baseline and ouab(max) I(SC) after injury with 500 microM H(2)O(2). We conclude that overexpression of the beta(1) subunit of the Na,K-ATPase may help maintain normal levels of vectorial Na(+) transport across ATII cell monolayers in pathologic conditions.


Subject(s)
Hydrogen Peroxide/pharmacology , Respiratory Mucosa/physiology , Sodium-Potassium-Exchanging ATPase/metabolism , Sodium/metabolism , Amphotericin B/pharmacology , Animals , Biological Transport, Active/drug effects , Biological Transport, Active/physiology , Cells, Cultured , DNA, Complementary , Fetus , Lung/cytology , Lung/physiology , Ouabain/pharmacology , Oxidants/pharmacology , Protein Subunits , Rats , Respiratory Mucosa/cytology , Respiratory Mucosa/drug effects , Sodium-Potassium-Exchanging ATPase/genetics , Transfection
19.
Am J Perinatol ; 17(1): 1-9, 2000.
Article in English | MEDLINE | ID: mdl-10928597

ABSTRACT

High-frequency ventilation (HFV) has been advocated to reduce lung injury and chronic lung disease (CLD) in preterm infants. Several randomized controlled trials have compared HFV with conventional mechanical ventilation (CMV) in preterm and term infants. This review first discusses animal data pertinent to optimizing the application of HFV in preterm infants. Second, a meta-analysis of all randomized controlled trials using HFV as an early intervention is presented. Finally, rescue use of HFV in preterm and term infants with respiratory failure or air leak syndromes is summarized. Eleven trials of early intervention with HFV are included in the meta analysis. Overall, chronic lung disease at 36 weeks postmenstrual age was reduced in patients treated with HFV, but mortality was not changed. The decrease in CLD, however, is confounded, as it is only based on small trials, whereas no pulmonary benefit was found in the three largest trials. Furthermore, HFV appears to increase the incidence of severe intracranial hemorrhages and periventricular leukomalacia. Therefore, routine elective use of HFV cannot be recommended at the present time. Limited data on rescue use of HFV suggest some benefits over continued CMV.


Subject(s)
High-Frequency Ventilation , Infant, Premature, Diseases/therapy , Lung Diseases/therapy , Bronchopulmonary Dysplasia/therapy , Chronic Disease , Humans , Infant, Newborn , Infant, Premature , Odds Ratio , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome, Newborn/therapy , Treatment Outcome
20.
Crit Care Med ; 28(6): 2064-8, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10890665

ABSTRACT

OBJECTIVES: High-frequency oscillatory ventilation (HFOV) with a high lung volume strategy is an experimental mode of ventilating preterm infants aimed at achieving maximal alveolar recruitment Higher mean airway pressures are used during HFOV than during intermittent positive-pressure ventilation (IPPV), and the intrathoracic volume increase is relatively constant. Both factors increase the risk to depress organ blood flow and diuresis. Our objective was to test the hypothesis that high lung volume HFOV attenuates the postnatal reduction of extracellular volume in preterm infants by reducing plasma atrial natriuretic factor and diuresis. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: University hospital, Level III neonatal intensive care unit. PATIENTS: Premature infants <30 wks gestation requiring intubation for respiratory distress syndrome within the first 6 hrs of life; 15 infants (gestational age, 26 [24-29] wks, birth weight 814 [452-1340] g) were randomized to HFOV, 19 infants (gestational age 27 [24-39] wks, birth weight 930 [644-1490] g) to IPPV. INTERVENTIONS: The randomized mode of ventilation was assigned within 1 hr after intubation. During HFOV mean airway pressure was increased as long as oxygenation improved and no lung overinflation was seen on chest radiograph. IPPV rates were > or =60/min. MEASUREMENTS AND MAIN RESULTS: We measured extracellular volume (sucrose dilution) and atrial natriuretic factor on Day 1 and Day 3. Mean airway pressure, body weight, diuresis, and fluid intake were measured daily. During HFOV mean airway pressure was higher at 12 hrs (median 7 cm H2O vs. 4 cm H2O; p = .001) and 24 hrs (median 6 cm H2O vs. 3 cm H2O; p = .01). In both groups, extracellular volume decreased between Day 1 and Day 3 (HFOV from 428 +/- 126 mL to 344 +/- 145 mL [p = .003], IPPV from 466 +/- 108 mL to 414 +/- 124 mL [p = .01]) and diuresis increased (HFOV, from 2.5 +/- 1.7 to 4.6 +/- 0.9 mL/kg/hr [p = .001]; IPPV, from 2.8 +/- 1.6 to 4.2 +/- 1.0 mL/kg/hr [p = .01]). Plasma atrial natriuretic factor was not decreased in the HFOV group. CONCLUSIONS: High lung volume HFOV as primary mode of ventilation in preterm infants <30 wks gestation did not result in unwanted fluid retention and a decrease in diuresis in the first days of life.


Subject(s)
Atrial Natriuretic Factor/blood , Diuresis/physiology , Extracellular Space , High-Frequency Ventilation , Infant, Premature , Intermittent Positive-Pressure Ventilation , Respiratory Distress Syndrome, Newborn/therapy , Gestational Age , Humans , Infant, Newborn , Prospective Studies , Respiratory Distress Syndrome, Newborn/blood , Respiratory Distress Syndrome, Newborn/physiopathology
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