The affinity of three substrates for the intestinal peptide carrier is explained based on their three-dimensional (3D) structural data. The kinetic transport parameters of three ACE-inhibitors, enalapril, enalaprilat, and lisinopril, have been determined in an in vivo system using rat intestine. The observed kinetic transport parameters (+/- asymptotic standard error) of enalapril are: 0.81 (+/- 0.23) mM, 0.58 (+/- 0.37) mumol/h per cm2, and 0.56 (+/- 0.04) cm/h for the half-maximal transport concentration (KT), the maximal transport flux (Jmax) and the passive permeability constant (Pm). Enalaprilat was transported by passive diffusional with a Pm of 0.51 (+/- 0.04) cm/h. For lisinopril the kinetic transport parameters were 0.38 (+/- 0.19) mM, 0.12 (+/- 0.07) mumol/h per cm2, and 0.18 (+/- 0.02) cm/h for KT, Jmax, and Pm, respectively. The affinity of the ACE-inhibitors for the intestinal peptide carrier has been evaluated based on their ability to inhibit the transport rate of cephalexin. The inhibition constants (Ki) of enalapril, enalaprilat and lisinopril were 0.15, 0.28 and 0.39 mM, respectively. 3D structural analysis of lisinopril using molecular modelling techniques reveals that intramolecular hydrogen bond formation is responsible for decreased carrier affinity.

The use of minimized extracorporeal circuits (MECC) in cardiac surgery is an important measure to increase the biocompatibility of cardiopulmonary bypass during coronary artery bypass grafting (CABG). These circuits eliminate volume storage reservoirs and bubble traps to minimize the circuit. However, the reduction in volume may increase the risk of gaseous microemboli (GME). The MECC system as used by our group consists of a venous bubble trap, centrifugal pump, and an oxygenator. To further reduce the risk of introducing GME, an oxygenator with an integrated arterial filter was developed based on the concept of minimal volume and foreign surface. We studied the air removal characteristics of this oxygenator with and without integrated arterial filter. The quantity and volume of GME were measured with precision at both the inlet and outlet of the devices. Our results showed that integration of an arterial filter into this oxygenator increased GME reducing capacity from 69.2% to 92%. Moreover, we were able to obtain data on the impact of an arterial filter on the exact size-distribution of GME entering the arterial line. The present study demonstrates that an MECC system and oxygenator with integrated arterial filter significantly reduces the volume and size of GME. The use of an integrated arterial filter in an MECC system may protect the patient from the deleterious effects of CPB and may further improve patient safety.

Objective To compare a continuous suture technique with interrupted stitches using inverted knots for postpartum perineal repair of second-degree lacerations and episiotomies.Design A double-blind randomised controlled trial.Setting A Danish university hospital with more than 4800 deliveries annually.Population A total of 400 healthy primiparous women with a vaginal delivery at term.Method Randomisation was computer-controlled. Structured interviews and systematic assessment of perineal healing were performed by research midwives blinded to treatment allocation at 24-48 hours, 10 days and 6 months postpartum. Pain was evaluated using a visual analogue scale and the McGill Pain Questionnaire. Wound healing was evaluated using the REEDA scale and by assessment of gaping wounds >0.5 cm. Analysis complied with the intention-to-treat principle.Main outcome measures The primary outcome was perineal pain 10 days after delivery. Secondary outcomes were wound healing, patient satisfaction, dyspareunia, need for resuturing, time elapsed during repair and amount of suture material used.Results A total of 400 women were randomised; 5 women withdrew their consent, leaving 395 for follow up. The follow-up rate was 98% for all assessments after delivery. No difference was seen in perineal pain 10 days after delivery. No difference was seen in wound healing, patient satisfaction, dyspareunia or need for resuturing. The continuous suture technique was significantly faster (15 versus 17 minutes, P = 0.03) and less suture material was used (one versus two packets, P < 0.01).Conclusion Interrupted, inverted stitches for perineal repair leaving the skin unsutured appear to be equivalent to the continuous suture technique in relation to perineal pain, wound healing, patient satisfaction, dyspareunia and need for resuturing. The continuous technique, however, is faster and requires less suture material, thus leaving it the more cost-effective of the two techniques evaluated.

The use of minimized extracorporeal circuits (MECC) in cardiac surgery is expanding. These circuits eliminate volume storage and bubble trap reservoirs to minimize the circuit. However, this may increase the risk of gaseous micro emboli (GME). To reduce this risk, a venous bubble trap was designed. This study was performed to evaluate if incorporation of a venous bubble trap in a MECC system as compared to our standard minimized extracorporeal circuit without venous bubble trap reduces gaseous micro emboli during cardiopulmonary bypass (CPB). Forty patients were randomly assigned to be perfused either with or without an integrated venous bubble trap. After preliminary evaluation of the data of 23 patients, the study was terminated prior to study completion. The quantity and volume of GME were significantly lower in patients perfused with a venous bubble trap compared to patients perfused without a venous bubble trap. The present study demonstrates that a MECC system with a venous bubble trap significantly reduces the volume of GME and strongly reduces the quantity of large GME (>500 µm). Therefore, the use of a venous bubble trap in a MECC system is warranted.

Introduction Recent studies demonstrated that irreversible electroporation (IRE) ablation may be an alternative method for thermal ablation for pulmonary vein isolation. Development of gaseous microemboli during catheter ablation might lead to asymptomatic ischemic events and is therefore an important research topic. Gas formation during arcing with direct current catheter ablation has been studied in the past, however not for nonarcing IRE‐ablation. Objective The aim of the present study was to visualize, quantify, and characterize gas formation during nonarcing millisecond IRE‐pulses using a multielectrode circular catheter. Methods In vitro, gas formation during IRE‐pulses was studied using a high‐speed imaging, direct volume measurements, and a bubble counter. Gas formation was compared between cathodal and anodal IRE‐pulses and between a small and large catheter hoop diameter. Results High‐speed images showed the location and dynamics of gas formation during cathodal and anodal millisecond IRE‐pulses. The direct volume measurements demonstrated a significantly larger volume for cathodal than for anodal IRE‐pulses (P < .001), and no significant difference between small and large hoop diameters. A strong linear relationship was found between delivered charge and total gas volume (r = 0.99). Bubble counter measurements showed that cathodal IRE‐pulses produced more and larger gas bubbles than anodal IRE‐pulses. The ratio of total gas volume between cathodal and anodal IRE‐pulses is different as predicted from electrolysis theory. Conclusion In vitro, millisecond anodal IRE‐pulses produce significantly less and smaller gas bubbles than millisecond cathodal IRE‐pulses. In vivo experiments are required to investigate the clinical implication of these observations.