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Marilette Stehouwer, Ward R Bijlsma, Allegonda Van der LelijDepartment of Ophthalmology, University Medical Center Utrecht, Utrecht, The NetherlandsPurpose: To investigate a possible association between Fuchs’ endothelial corneal dystrophy (FECD) and hearing disability.Methods: A cross-sectional observational study was performed at the University Medical Center Utrecht. Cases and controls were patients who were treated by a cornea specialist between 2004 and 2008. FECD patients had either already undergone or were planned for a keratoplasty procedure. All controls were patients treated for cataract without any corneal pathology. Cases and controls were matched by age group and gender. A structured telephone interview combined with a validated self-perceived hearing function test (the Hearing Handicap Inventory for the Elderly, screening version; HHIE-S) was used for data collection.Results: Hearing disability was reported in 33 patients (45.8%) in the FECD-group (n = 72, average age: 73 years) versus 50 patients (34.7%) in the control group (n = 144, average age: 73 years). Hearing disability was significantly associated with FECD after adjustment for age, noise exposure, and diabetes mellitus (odds ratio 1.97 95% confidence interval 1.04–3.75).Conclusion: This case–control study reports a significant association between FECD and hearing disability. The causal relation was not evaluated in this study, though mutations in the SLC4A11 gene could have played an important role. This gene encodes for an ion transporter, which has been found in the cornea and inner ear. With the lack of examination with a pure tone or speech audiometry in this study, further studies need to be performed in order to support the association and should include a complete ENT examination with audiometry and genetic research.Keywords: hearing disability, hearing impairment, Fuchs’ endothelial corneal dystrophy

PurposeWith a new Fourier domain optical coherence tomography (FD OCT) device, SL SCAN-1 (Topcon Europe Medical BV, Capelle a/d IJssel, The Netherlands), integrated into a slit-lamp OCT, scans can be obtained through a handheld lens. The necessary adjustment of the reference arm is possible by fast Z-alignment. This study was performed to prove the capability of SL SCAN-1 to scan through a three-mirror contact lens, scanning the peripheral retina and anterior chamber angle.MethodsDifferent representative pathologies of the peripheral retina and anterior chamber were simultaneously observed and scanned with the SL SCAN-1. The scans of peripheral retinal lesions were obtained both through a handheld lens and through a three-mirror contact lens. The anterior chamber angle was scanned directly with the SL SCAN-1 in anterior mode, and through the gonio-mirror of a three-mirror contact lens with the SL SCAN-1 in posterior mode.ResultsOCT scans could be obtained with the SL SCAN-1 of the peripheral retina through both, a common handheld lens and a three-mirror contact lens. The scans obtained through a three-mirror contact lens were of better quality, visualizing details of the different layers of the retina more clearly. The scans of the anterior chamber, obtained through the gonio-mirror of a three-mirror contact lens, visualized the open anterior chamber angle, with details of fine structures.ConclusionsThe SL SCAN-1 is a unique FD OCT system, which is able to scan not only the posterior pole and anterior segment but also the anterior chamber angle and the more peripheral retina. These four modalities combined into one device could make the SL SCAN-1 a very powerful aid in daily practice. [ABSTRACT FROM AUTHOR]

PurposeFourier Domain Optical Coherence Tomography (FD-OCT) provides high resolution cross-sectional images of the retina and the anterior segment. It has become an important tool in ophthalmology in the examination, diagnosis, and treatment of important and common diseases. Present OCT imaging systems are stand-alone devices. The aim of this paper is to show the quality of images made with a prototype of a Fourier Domain (FD-) OCT imaging system (SLSCAN-1) integrated into a slit lamp.MethodsDifferent representative pathologies of the posterior and anterior segment were observed with the slit lamp and simultaneously scanned with a prototype of the slit lamp-integrated FD-OCT system. The clinical interpretation of posterior segment images made with the prototype were compared to those obtained with a stand-alone FD-system (3D-OCT-1000 Mark II, Topcon).ResultsImages made with the slit lamp-integrated FD-OCT were of sufficient quality to allow for a correct interpretation of the observed pathological conditions. Conclusions based on the images of the posterior segment of the prototype were identical to the conclusions based on the images of a stand-alone FD-system (3D-OCT-1000 Mark II, Topcon). In addition to the images of the posterior segment, images could be made of the anterior segment. The OCT system did not interfere with the normal functionality of the slit lamp.ConclusionThe slit lamp-integrated FD-OCT system provided high quality images of both the anterior and the posterior segment. Scans made with the slit lamp-integrated FD-OCT system could be of use in clinical practice. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) remains a leading cause of vision loss in the geriatric population. There are age-related changes in peripheral blood leukocyte composition, but their significance for AMD remains unclear. We aimed to determine changes in immune cell populations in the blood of AMD patients. A standardized 31-parameter flow cytometry analysis was conducted on peripheral blood mononuclear cells from 59 patients with early and advanced AMD and 39 controls without AMD, all older than 65 years. Fundus photography and optical coherence tomography were used to classify disease stages and a custom genotype array was used to compute an AMD genetic risk score based on 52 AMD disease risk variants (GRS-52). A generalized linear regression model corrected for age, sex, and smoking status revealed that AMD patients showed decreased frequencies of CD4 + T helper cell population expressing Integrin Alpha E (CD103) (Padj = 0.019). We further noted that early AMD was characterized by increased interleukin-4 (IL-4)-producing CD4 + T helper cells (Padj = 0.013; <0.001), as well as IL-4-producing cytotoxic CD8 + T cells (Padj = 0.016; <0.001). Reclassification of samples based on the GRS-52 revealed that IL-17-producing T cells decreased incrementally across GRS-52 categories. In AMD, alterations in peripheral blood leukocyte populations are associated with genetic risk score and disease stage and include specifically IL-4 and IL-17A cytokine-producing and CD103 integrin-expressing T cell populations., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: During cardiac surgery the use of a minimal extracorporeal circulation (MiECC) system may reduce the adverse effects for the patient. This is probably caused by reduced inflammation and hemodilution. For the use of a MiECC circuit, a venous bubble trap (VBT) is warranted for safety reasons. The aim of this study was to assess if an arterial filter with a small prime volume has the same (or better) air removal capacities as a VBT in a MiECC circuit and subsequentially may be used as an alternative., Methods: In an in vitro study, air removal properties were compared between the arterial filter and three VBT's on the market, VBT160 (Getinge), VBT 8 (LivaNova and VARD (Medtronic). In a MiECC circuit, the filter devices were placed in a venous position and challenged with massive and micro air. Gaseous microemboli (GME) were measured with a bubble counter proximal and distal of the VBT device., Results: More than 99.9 % of the air was removed after a bolus air challenge by all VBT's. Both the VARD and the AF100 showed better GME removal properties (not significant for the AF100) compared to the other devices. All filters showed GME generation after a challenge with massive air. Compared to the other filters, only the VARD showed no passing of larger bubbles when a volume of 50 mL of air was present in the filter., Conclusions: The AF100 seems to be a safe and low prime alternative for use in a MiECC system as a venous air trap. A word of caution, placement of the AF100 arterial filter in the venous line is off label use., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Oxygenators, as used in cardiopulmonary bypass (CPB) circuits, are components with good air removal properties. However, under some conditions the semipermeable characteristics of hollow fibers allow air to accidentally enter the blood side of the CPB circuit. This may occur when a fluid in motion is stopped suddenly by which the rapid change in momentum may cause a relative negative pressure drop, the so-called hammer effect. The hammer effect is not yet described in literature related to CPB. The aim of this in vitro study was to reproduce the hammer effect., Methods: The in vitro setup consisted of a CPB circuit with a fully occluded roller pump and one of four test oxygenators. The hammer test was performed by a sudden pump stop. The pressure wave was measured and after the test the residual air present in the oxygenator was forced into the arterial line and measured with a bubble detector., Results: We showed that a sudden pump stop could lead to the hammer effect, represented as a relative negative pressure drop in the arterial line. This hammer effect resulted in air release through the semipermeable fibers as we showed in two of the four tested brands of oxygenators., Conclusions: We conclude that the hammer effect may occur before connection of the CPB system to the patient, and this may result in air release into the arterial blood side of the oxygenator. The hammer effect can be caused by clamping of the tubing in combination with a centrifugal pump, or by suddenly stopping the roller pump. With this study we would like to raise awareness of the hammer effect., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The landmark 2016 Minimal Invasive Extracorporeal Technologies International Society (MiECTiS) position paper promoted the creation of a common language between cardiac surgeons, anesthesiologists and perfusionists which led to the development of a stable framework that paved the way for the advancement of minimal invasive perfusion and related technologies. The current expert consensus document offers an update in areas for which new evidence has emerged. In the light of published literature, modular minimal invasive extracorporeal circulation (MiECC) has been established as a safe and effective perfusion technique that increases biocompatibility and ultimately ensures perfusion safety in all adult cardiac surgical procedures, including re-operations, aortic arch and emergency surgery. Moreover, it was recognized that incorporation of MiECC strategies advances minimal invasive cardiac surgery (MICS) by combining reduced surgical trauma with minimal physiologic derangements. Minimal Invasive Extracorporeal Technologies International Society considers MiECC as a physiologically-based multidisciplinary strategy for performing cardiac surgery that is associated with significant evidence-based clinical benefit that has accrued over the years. Widespread adoption of this technology is thus strongly advocated to obtain additional healthcare benefit while advancing patient care., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Kyriakos Anastasiadis: Consulting agreement with Medtronic. Polychronis Antonitsis: Consulting agreement with Medtronic. Aschraf El-Essawi: Consulting agreement with Medtronic, speaker for Terumo and Edwards. Andreas Liebold: Consulting agreement with Edwards Lifesciences, educational grants from Getinge, LivaNova and Abbott. Bob Kiaii: Consulting agreement with Medtronic, Abbott, and Johnson and Johnson. Adrian Bauer: Advisory board of LivaNova, speaker for Köhler Chemie, advertisement and studies for Medtronic. Wim van Boven: Consulting agreement with Medtronic Helena Argiriadou: Consulting agreement with Medtronic. Hansjoerg Jenni: Consulting agreement with Medtronic. Marco Di Eusanio: Consulting agreement with Medtronic, Corcym and Edwards. Christophe Baufreton: Consulting agreement with Medtronic, Liva-Nova, Nordic Pharma and Cytosorbents. Ignazio Condello: Consulting agreement with Eurosets and Livanova. Marco Ranucci: Advisory Board Member for Medtronic and Livanova. All other authors declared no conflict of interest.

Aims: Irreversible electroporation (IRE) ablation is a non-thermal ablation method based on the application of direct current between a multi-electrode catheter and skin electrode. The delivery of current through blood leads to electrolysis. Some studies suggest that gaseous (micro)emboli might be associated with myocardial damage and/or (a)symptomatic cerebral ischaemic events. The aim of this study was to compare the amount of gas generated during IRE ablation and during radiofrequency (RF) ablation., Methods and Results: In six 60-75 kg pigs, an extracorporeal femoral shunt was outfitted with a bubble-counter to detect the size and total volume of gas bubbles. Anodal and cathodal 200 J IRE applications were delivered in the left atrium (LA) using a 14-electrode circular catheter. The 30 and 60 s 40 W RF point-by-point ablations were performed. Using transoesophageal echocardiography (TOE), gas formation was visualized. Average gas volumes were 0.6 ± 0.6 and 56.9 ± 19.1 μL (P < 0.01) for each anodal and cathodal IRE application, respectively. Also, qualitative TOE imaging showed significantly less LA bubble contrast with anodal than with cathodal applications. Radiofrequency ablations produced 1.7 ± 2.9 and 6.7 ± 7.4 μL of gas, for 30 and 60 s ablation time, respectively., Conclusion: Anodal IRE applications result in significantly less gas formation than both cathodal IRE applications and RF applications. This finding is supported by TOE observations., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: To evaluate the long-term follow-up of patients with a circumscribed choroidal hemangioma (CCH) treated with limited single spot photodynamic therapy (PDT) at the Amsterdam University Medical Center, location AMC (AUMC)., Methods: This cross-sectional study included 17 patients, treated between 2001 and 2012. Evaluation included best corrected visual acuity, slitlamp examination, fundoscopy, ophthalmic ultrasonography (USG), fluorescein/indocyanine green angiography (FA/ICG), fundus autofluorescence (FAF) and optical coherence tomography (OCT)., Primary Outcome: recurrence rate, secondary outcomes: long-term functional and structural changes., Results: An unexpected high recurrence rate of 35% (n6) was found with a mean follow-up time between treatment and recurrence of almost 6 years, range 2.8-10.7 years. With a recurrence, the classical CCH pattern was no longer recognizable on FA or ICG. Signs of leakage were best observed with OCT, and the recurrence could be confirmed with USG. Retreatment with PDT of all recurrences was successful. After a successful initial PDT, the achieved visual acuity (VA) showed a small decrease over time, median VA from 0.10 LogMar to 0.15 LogMar (p 0.09) after a mean follow-up of 11.36 years (range 5.1-15.5 years). During follow-up study visit, the OCT revealed a slightly increased thickness of the choroid in 86% of cases at the site of the original tumour, without a clear correlation to the recurrences., Conclusion: Limited single spot PDT is a safe and effective treatment for CCH preserving a good VA. However, because of the relatively high recurrence rate found in this study, we recommend regular follow-up with OCT every 6 months., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

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., (© 2019 Wiley Periodicals, Inc.)

Objective: Here we describe a rare case of systemic sarcoidosis in a healthy young man with neuroborreliosis as a putative trigger., Case: A 21-year-old forestry worker was diagnosed with systemic sarcoidosis involving his lungs, kidneys and skin. Additional diagnostics revealed signs indicative of a recent infection with Borrelia burgdorferi . The patient was treated successfully with prednisolone and antibiotics., Conclusion: Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. This case suggests that an infection with B. burgdorferi , the causal agent of Lyme disease, could act as a trigger for sarcoidosis., Learning Point: We should maintain a high index of suspicion for underlying infectious processes like neuroborreliosis in patients with new-onset sarcoidosis before starting immunosuppressive regimens., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests.

Purpose: A peripheral senile retinoschisis is sometimes difficult to distinguish from a retinal detachment by biomicroscopy alone. This study evaluated spectral domain OCT (SD-OCT) scans of the far peripheral retina to improve the differentiation between these diseases., Methods: Patients were included in whom the distinction between retinal detachment and senile retinoschisis was not clear based on biomicroscopy alone, or who had a presumed clinical diagnosis of senile retinoschisis. OCT scans were made with the SLSCAN-1, through a hand-held lens and a 3-mirror contact lens, while the area of interest was simultaneously observed with the slit lamp. The SLSCAN-1 is a SD-OCT integrated into a slit lamp, superluminescent diode light source with a central wavelength of 830 nm, bandwidth 30 nm, scan resolution 8-9 μm in tissue, scan depth 2 mm, scan speed 5000 A-scans per second., Results: In the 11 patients with an uncertain diagnosis, OCT scans showed a senile retinoschisis in four and a retinal detachment in seven patients. Fifteen of the 18 patients with a presumed diagnosis of retinoschisis showed a retinoschisis on OCT. In five of them, the OCT scans revealed a schisis detachment. Interestingly, three of the 18 patients had a retinal detachment., Conclusion: Senile retinoschisis may mimic a peripheral retinal detachment and vice versa. Differentiation is important with respect to therapeutic decisions. OCT scans of the far peripheral retina, which can be made with the SLSCAN-1 through a 3-mirror contact lens, can contribute significantly to this differentiation. The obtained scans of the far peripheral retina clearly visualize the anatomic differences between both diseases., (© 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: The purpose of this study was to model the influence of cataract on Spectral Domain Optical Coherence Tomography (SDOCT) image quality and Retinal Nerve Fibre Layer (RNFL) thickness measurements., Methods: SDOCT images, made with two different devices (3DOCT-1000, Topcon and Cirrus HD-OCT), before and after cataract surgery were compared and judged against measurements from normal subjects using artificial filters simulating the effects of cataract. Optical density of the images was calculated based on a mathematical model described previously., Results: In total, forty-eight eyes were included for pre- and postoperative cataract extraction measurements. OCT image quality significantly (p < 0.001) improved postoperative and postoperative RNFL thickness was significantly (p < 0.001) thicker in both groups of patients. The measurements using artificial filters showed a rather precise linear relation between change in filter induced optical density and change in RNFL thickness (R = 0.941, p < 0.001 for 3DOCT-1000 and R = 0.785, p < 0.001 for Cirrus HD-OCT). For the patient groups, the relation was less marked, 3DOCT-1000 Rs = 0.697, p < 0.03 and Cirrus HD-OCT Rs = 0.444, p < 0.03. The predictive potential based on the found linear relationship between OCT-effective optical density of cataract and the cataract-induced underestimation was however limited, and mean difference ± SD between predicted and measured RNFL thickness were 1.68 ± 7.55 (3DOCT-1000) and 3.71 ± 2.97 (Cirrus HD-OCT) micron., Conclusions: A linear relationship exists between OCT-effective optical density of cataract and underestimation of RNFL thickness measured with OCT. This finding holds promise to correct for cataract-induced changes in RNFL measurements, but will differ for each type of OCT device., (© 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.)

Purpose: The purpose of this study was to determine whether diabetes type 2 causes thinning of retinal layers as a sign of neurodegeneration and to investigate the possible relationship between this thinning and duration of diabetes mellitus, diabetic retinopathy (DR) status, age, sex, and glycemic control (HbA1c)., Methods: Mean layer thickness was calculated for retinal layers following automated segmentation of spectral domain optical coherence tomography images of diabetic patients with no or minimal DR and compared with controls. To determine the relationship between layer thickness and diabetes duration, DR status, age, sex, and HbA1c, a multiple linear regression analysis was used., Results: In the pericentral area of the macula, the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) were thinner in patients with minimal DR compared to controls (respective difference 1.9 μm, 95% confidence interval [CI] 0.3-3.5 μm; 5.2 μm, 95% CI 1.0-9.3 μm; 4.5 μm, 95% CI 2.2-6.7 μm). In the peripheral area of the macula, the RNFL and IPL were thinner in patients with minimal DR compared to controls (respective difference 3.2 μm, 95% CI 0.1-6.4 μm; 3.3 μm, 95% CI 1.2-5.4 μm). Multiple linear regression analysis showed DR status to be the only significant explanatory variable (R = 0.31, P = 0.03) for this retinal thinning., Conclusions: This study demonstrated thinner inner retinal layers in the macula of type 2 diabetic patients with minimal DR than in controls. These results support the concept that early DR includes a neurodegenerative component.

Diabetic retinopathy (DR) classically presents with micro-aneurysms, small haemorrhages and/or lipoprotein exudates. Several studies have indicated that neural loss occurs in DR even before vascular damage can be observed. This study evaluated the possible relationship between structure (spectral domain-optical coherence tomography) and function (Rarebit visual field test) in patients with type 1 diabetes mellitus and no or minimal diabetic retinopathy (DR). Results demonstrated loss of macular visual function and corresponding thinning of the ganglion cell layer (GCL) in the pericentral area of the macula of diabetic patients (Rs = 0.65, p < 0.001). In multivariable logistic regression analysis, GCL thickness remained an independent predictor of decreased visual function (OR 1.5, 95% CI 1.1-2.1). Early DR seems to include a neurodegenerative component., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

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.

Purpose: The objective of this study was to determine the influence of the peptide bond with emphasis on the carbonyl group on the interaction with and transport by the intestinal small-peptide carrier. Therefore enalapril, a known substrate for the small-peptide carrier, has been modified to an analogue with a reduced peptide bond, enamipril. The transport characteristics of both compounds have been determined., Methods: The in vitro transport studies were performed using rat ileum in Ussing chambers. The transport of enalapril and enamipril were measured in a concentration range from 0.5-8 mM in both directions across the ileum. in the presence and absence of inhibitors. The interaction with the small-peptide carrier was studied by evaluating the ability of enalapril and its analogue enamipril to inhibit the transport rate of amoxycillin., Results: Enalapril shows, besides passive diffusion (P(m)3.06+/-0.14 . 10(-6)cm/s), saturable transport kinetics (Jmax = 16+/-5 nmol/h.cm2, Km = 1.86+/-0.64 mM) which can be inhibited with 10 mM cephalexin. The analogue with a reduced peptide bond does not show saturable transport from the mucosal to the serosal side, and cephalexin does not inhibit the flux of enamipril. However, the transport of enamipril from the serosal to mucosal side of the intestinal membrane is saturable and can be inhibited by 100 microM verapamil. Although enamipril is not a substrate for the small-peptide carrier in contrast to enalapril, both enalapril and enamipril are able to inhibit the active transport of amoxycillin with a K(i) of 0.41+/-0.24 mM and 0.24+/-0.12 mM respectively., Conclusions: The reduction of the peptide bond of enalapril results in a compound, enamipril, which does not show polarized and saturable transport from the mucosal to the serosal side of the intestinal tissue. Also because the transport of enamipril cannot be inhibited by cephalexin, the analogue with the reduced peptide bond is no longer a substrate for the intestinal small-peptide carrier. Therefore, it can be concluded that the carbonyl group is an essential structural requirement for transport by the small-peptide carrier. In contrast, the interaction with the small-peptide carrier is still present, shown by the inhibition of the fluxes of amoxycillin. Reduction of the peptide bond of enalapril resulted in a new substrate for the P-glycoprotein efflux pump.

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.

A case of euthyroid hypothyroxinaemia caused by the interference of the patient's serum with the Abbott thyroxine TDx assay is reported. This cause of falsely low serum thyroxine levels is probably rare but possibly underrecognized. Clinical implications are discussed.