[Prevalence of Gastroschisis, Omphalocele, Spina Bifida and Orofacial Clefts of Neonates from January 2000 to December 2010 in Leipzig, Saxony, Saxony-Anhalt and Germany]. / Prävalenz von Gastroschisis, Omphalozele, Spina bifida und orofazialen Spaltbildungen bei Neugeborenen im Zeitraum Januar 2000­Dezember 2010 in Leipzig, Sachsen, Sachsen-Anhalt und Deutschland.

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.

[Head and Neck Cancer in Pregnancy - Recommendations for Diagnosis and Therapy With Case Report]. / Kopf-Hals-Krebs in der Schwangerschaft ­ Empfehlungen zu Diagnostik und Therapie mit Fallbericht.

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.

Cesarean section increases the risk of respiratory adaptive disorders in healthy late preterm and two groups of mature newborns.

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.

[Prediction of extubation failure in ELBW preterm infants]. / Prädiktion von Extubationsversagen bei ELBW-Frühgeborenen.

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.

Blood group AB increases risk for surgical necrotizing enterocolitis and focal intestinal perforation in preterm infants with very low birth weight.

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.

Nonconvulsive status epilepticus in epileptic encephalopathies in childhood.

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.

Syntaxin 1A is expressed in airway epithelial cells, where it modulates CFTR Cl(-) currents.

The CFTR Cl(-) channel controls salt and water transport across epithelial tissues. Previously, we showed that CFTR-mediated Cl(-) currents in the Xenopus oocyte expression system are inhibited by syntaxin 1A, a component of the membrane trafficking machinery. This negative modulation of CFTR function can be reversed by soluble syntaxin 1A peptides and by the syntaxin 1A binding protein, Munc-18. In the present study, we determined whether syntaxin 1A is expressed in native epithelial tissues that normally express CFTR and whether it modulates CFTR currents in these tissues. Using immunoblotting and immunofluorescence, we observed syntaxin 1A in native gut and airway epithelial tissues and showed that epithelial cells from these tissues express syntaxin 1A at >10-fold molar excess over CFTR. Syntaxin 1A is seen near the apical cell surfaces of human bronchial airway epithelium. Reagents that disrupt the CFTR-syntaxin 1A interaction, including soluble syntaxin 1A cytosolic domain and recombinant Munc-18, augmented cAMP-dependent CFTR Cl(-) currents by more than 2- to 4-fold in mouse tracheal epithelial cells and cells derived from human nasal polyps, but these reagents did not affect CaMK II-activated Cl(-) currents in these cells.

Ventilation strategies and outcome in randomised trials of high frequency ventilation.

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.

The role of elevated central-peripheral temperature difference in early detection of late-onset sepsis in preterm infants.

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.

Effect of the TI/TE ratio on mean intratracheal pressure in high-frequency oscillatory ventilation.

In high-frequency oscillatory ventilation (HFOV), an adequate mean airway pressure is crucial for successful ventilation and optimal gas exchange, but air trapping cannot be detected by the usual measurement at the y piece. Intratracheal pressures produced by the high-frequency oscillators HFV-Infantstar (IS), Babylog 8000 (BL), and the SensorMedics 3100A (SM) [the latter with either 30% (SM30) or 50% (SM50) inspiratory time] were investigated in four anesthetized tracheotomized female piglets that were 1 day old and weighed 1.6-1.9 kg (mean 1.76 kg). The endotracheal tube was repeatedly clamped while the piglets were ventilated with an oscillation frequency of 10 Hz, and the airway pressure distal of the clamp was recorded as a measure of average intrapulmonary pressure during oscillation. Clamping resulted in a significant decrease of mean airway pressure when the piglets were ventilated with SM30 (-0.86 cmH2O), BL (-0.66 cmH2O), and IS (-0.71 cmH2O), but airway pressure increased by a mean of 0.76 cmH2O with SM50. Intratracheal pressure, when measured by a catheter pressure transducer at various oscillation frequencies, was lower than at the y piece by 0.4-0.9 cmH2O (SM30), 0.3-3 cmH2O (BL), and 1-4.7 cmH2O (IS) but was 0.4-0.7 cmH2O higher with SM50. We conclude that the inspiratory-to-expiratory time (TI/TE) ratio influences the intratracheal and intrapulmonary pressures in HFOV and may sustain a mean pressure gradient between the y piece and the trachea. A TI/TE ratio < 1:1 may be useful to avoid air trapping when HFOV is used.

Pharmacokinetics of two different delivery regimens of doxorubicin in isolated hyperthermic limb perfusion.

Evaluation of doxorubicin (DOX) pharmacokinetics in hyperthermic isolated limb perfusion (HILP) is limited. In this study two administration regimens of DOX were compared in terms of area under the time concentration curve (AUC) in plasma. HILP was performed in 13 dogs. In group 1 (n = 7) four single doses of DOX were injected in intervals of 15 minutes, in group 2 (n = 6) DOX was administered continuously during the first 30 min. The total dose in both groups was 1 mg/kg body weight, and the perfusion lasted 60 min. Concentrations of DOX and its major metabolite doxorubicinol (DOXol) were measured in perfusate and muscle tissue by high performance liquid chromatography (HPLC). Pharmacokinetic estimates were calculated. The two investigated administration modes provided sufficient drug levels of DOX during the whole perfusion time. Maximum concentrations in the perfusate and areas under the time concentration curves were nearly the same. The tissue concentrations also did not show significant differences. Both regimens are practicable avoiding high peak levels of the drug in order to minimize toxic side effects.

Tissue toxicity of doxorubicin in first and second hyperthermic isolated limb perfusion--an experimental study in dogs.

The aim of this experimental study in dogs was to assess the tissue toxicity of doxorubicin (DOX) and the impact of dose and pharmacokinetics after double isolated limb perfusion (ILP). Fifteen beagle dogs were assigned to three groups of five animals each. In the first ILP 0.75 mg/kg bodyweight (bw) DOX was given to all animals. In the second perfusion after an interval of 6 to 8 weeks the dosage was 0.5 mg/kg bw in group I, 0.75 mg/kg bw in group II, and 1.0 mg/kg bw in group III. At the same dosage tissue toxicity increased in comparison to the first ILP. At the second ILP there was a dose-toxicity relationship. At a dose of 0.75 mg/kg bw pharmacokinetics of DOX in the perfusate showed no significant differences between first and second perfusion. The mean muscle tissue levels during the second ILP were lower than during the first perfusion. However, in contrast to the first perfusion, they showed a further increase after perfusate eluation. A disturbed microcirculation caused by intima proliferations in arteries and arterioles fter the first ILP may impair the removal of DOX from the intravasal and interstitial compartment and can be assumed as a reason for increased tissue toxicity. Therefore, we recommend a reduction of DOX dose in the second ILP for clinical use.

Comparison of lung volume measurements by antero-posterior chest X-ray and the SF6 washout technique in mechanically ventilated infants.

While anterior/posterior chest x-rays (CXR) are routinely performed to estimate lung volume (LV) and adjust ventilator settings, the precise measurement of LV requires additional sophistication. In 31 infants ventilated because of surfactant deficiency (n=23), bronchopulmonary dysplasia (n=7), or pulmonary hypoplasia (n=1) with either intermittent positive pressure (n=18) or high frequency oscillation (n=13) (gestational age 23-39 weeks (median 26 weeks); birthweight 550-2780 g (median 840 g); age at measurement 1-91 days (median 6 days); weight at study time (WST) 675-3000 g (median 938 g)), we investigated whether LV, as measured by the sulfur hexafluoride (SF6) washout technique, could by estimated from CXR by: 1) the sum (A+B) of the right (A) and left (B) lung fields areas; 2) the product (LxW) of the distances from the right apex to the right costophrenic angle (L) and between both costophrenic angles (W); 3) the diaphragm position relative to the posterior parts of the ribs (DP); and 4) the lung radiolucency (RL, grades 0-4). Correlations between A+B (r=0.44) or LxW (r=0.37) and LV were poor, but improved when A+B, LxW, and LV were normalized to WST: (A+B)/WST vs. LV/WST (r=0.74), and LxW/WST vs. LV/WST (r=0.67). DP (r=0.13) and RL (Spearman's rho=0.17) did not correlate with LV/WST. A multiple linear regression analysis led to the following best-fit equation: LV/WST=2.58 (A+B)/WST - 5.47 DP + 42.2 (r=0.83). We concluded that an estimate of LV from CXR lacked sufficient accuracy. DP and RL did not correlate with LV measured by SF6 washout.

[Hepatolithiasis and Caroli's disease in Argentina: results of a multicenter study]. / Hepatolitiasis y enfermedad de Caroli en Argentina: resultados de un estudio multicéntrico.

The goal of this study was to determine the prevalence, epidemiology and clinical-therapeutical evolution of hepatolithiasis (HL) in Argentina. With this purpose a survey was conducted sending a questionnaire to ten referencial and interventional radiology centers in the country. Seven centers answered on time. In the last five years a total of 8,736 consecutive patients were examined for cholangiography (endoscopic retrograde cholangiography, PTC). A total of 5,920 (68%) were biliary lithiasis and 53 (0.9%, range 0.5-2.6%) of these were HL. In case of HL the diagnostic procedure was the ERCP in 68% of the cases, and the PTC in the remainder 32%. The patients with HL (53% females, mean age 52, range 23-85) clinically presented cholangitis (79%); pancreatitis (6%) and five (9.4%) showed evolution to a biliary cirrhosis. Associated diseases or abnormalities of the biliary tree were: biliary postsurgical strictures (BPS), 28%; Caroli's Syndrome, 20%; and choledocholithiasis, 28%. While a 9.4% presented a "biliary history" (that was defined as two or more episodes of biliary surgery) and a 5.7% lacked associated or predisposing diseases. Follow-up was lost in 23% of the cases and in 77% a follow up of 38 months (range 8-60) was observed with 4.8% mortality rate. The treatment was hepatobiliary surgery in 58% of the cases; endoscopic papillotomy in 17% and combined treatments that included extracorporeal shock wave lithotripsy and ursodeoxycholic acid (UDCA) in 15%. Four out of 53 cases (7.5%) received UDCA as the only successful therapy. HL is an entity with high biliary morbidity in 85% of the cases and development in to cirrhosis in 9.4%. When the diagnosis is made in the western world both BPS and Caroli must be discarded first. Combined treatments or only UDCA are new therapeutical alternative in the western world.

Hypertrophic intraventricular flow obstruction after very-low-dose dexamethasone (Minidex) in preterm infants: case presentation and review of the literature.

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.

Changes in regional tissue oxygenation saturation and desaturations after red blood cell transfusion in preterm infants.

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.

Benzimidazolones enhance the function of epithelial Na⁺ transport.

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.