Detecting signs of retinal leakage in exudative AMD using Cirrus OCT versus SL SCAN-1, a novel integrated FD-OCT into a common slit lamp.

PURPOSE: The purpose is to evaluate the interdevice and interobserver agreements between the SL SCAN-1 (a FD-OCT integrated into a common slit lamp) and a standard stand-alone FD-OCT device (the Cirrus) with regard to the presence or absence of signs of leakage in the retina in patients with exudative AMD and treated with anti-VEGF. METHODS: Fifty-six patients, known to have exudative AMD and under treatment with anti-VEGF agents, were included. During a regular follow-up, OCT scans were made with the Cirrus (macular-cube pattern) and the SL SCAN-1 (radial-scan pattern). All scans were graded by two medical retina specialists for signs of intraretinal cysts, subretinal fluid accumulation, and thickening of the neurosensory retina. Presence of signs of leakage was concluded if one or more of the three signs were present. RESULTS: In 91 % of the patients, the observers made identical conclusions for both devices of the presence of signs of leakage, resulting in an interdevice Kappa coefficient of 0.87. For the scans with disagreement about the presence or absence of signs of leakage, positive and negative conclusions were equally distributed between both devices, and differences were restricted to more subtle signs of leakage. CONCLUSION: The interdevice Kappa coefficient of 0.87 shows a high agreement between the SL SCAN-1 and the Cirrus in grading signs of leakage in exudative AMD. OCT images play a pivotal role in the diagnosis and management of exudative diseases like AMD, and the SL SCAN-1 provides a very efficient approach to these patients with the integration of the FD-OCT device into a common slit lamp.

Scanning beyond the limits of standard OCT with a Fourier domain optical coherence tomography integrated into a slit lamp: the SL SCAN-1.

PURPOSE: With 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. METHODS: Different 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. RESULTS: OCT 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. CONCLUSIONS: The 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.

Fourier Domain Optical Coherence Tomography integrated into a slit lamp; a novel technique combining anterior and posterior segment OCT.

PURPOSE: Fourier 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. METHODS: Different 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). RESULTS: Images 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. CONCLUSION: The 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.

Postpartum perineal repair performed by midwives: a randomised trial comparing two suture techniques leaving the skin unsutured.

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.

Combined bedtime insulin--daytime sulphonylurea regimen compared with two different daily insulin regimens in type 2 diabetes: effects on HbA1c and hypoglycaemia rate--a randomised trial.

BACKGROUND: Several efficacy studies of insulin-therapy regimens in patients with type 2 diabetes mellitus have shown varying results. Moreover, most studies did not address hypoglycaemia frequency and severity. METHODS: In this multicentre study, we compared the glycaemic efficacy and incidence rate of hypoglycaemic episodes between 3 treatment regimens in obese type 2 diabetic patients with secondary failure to sulphonylurea and metformin. During the run-in phase, patients were treated with glimepiride and metformin. After 3 months, 261 patients with HbA(1c) values >6.5% were randomised to (A) glimepiride + Neutral Protein Hagedorn (NPH) insulin at bedtime, (B) NPH insulin twice daily and (C) 30/70 mixture of short-acting and NPH insulin twice daily. The therapeutic aim was an HbA(1c) level < or =6.5%. RESULTS: Mean HbA(1c) achieved at 9 months was significantly higher in group A: 8.9% versus 8.3% and 8.4% in groups B and C, respectively (P < 0.001). There was no difference in the mild hypoglycaemic event rate, 0.36 versus 0.48 versus 0.53 events per patient month, in groups A, B and C, respectively. Severe hypoglycaemic events, requiring help from others, did not occur throughout the study. The mean weight gain and insulin dose were comparable in all three groups. CONCLUSIONS: The glimepiride + NPH insulin treatment resulted in a higher HbA(1c) level, as compared to the other regimens. In the clinical setting of this multicentre study, good glycaemic control was only achieved in a minority of the patients, irrespective of the applied regimen.

Structure-transport relationship for the intestinal small-peptide carrier: is the carbonyl group of the peptide bond relevant for transport?

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.

Molecular mechanism for the relative binding affinity to the intestinal peptide carrier. Comparison of three ACE-inhibitors: enalapril, enalaprilat, and lisinopril.

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.

Falsely low serum thyroxine levels caused by interference with the thyroxine assay.

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.