Decoding glaucoma module premium edition

Background:Traditional methods for neuroretinal rim width measurement in spectral domain optical coherence tomography (SD-OCT) employs the Bruch‘s membrane opening (BMO) as the anatomical border of the rim, referenced to a BMO horizontal reference plane, termed as “Bruch’s Membrane Opening-Horizontal Rim Width” (BMO-HRW). BMO-HRW is defined as the distance between BMO and internal limiting membrane (ILM) on the horizontal plane. In contrast, the Spectralis OCT (Heidelberg Engineering, Germany) employs a new parameter called “Bruch’s Membrane Opening–Minimum Rim Width” (BMO-MRW) with Glaucoma Module Premium Edition (GMPE). GMPE provides a novel objective method of optic nerve head (ONH) analysis using BMO, but the neuroretinal rim assessment is performed from the BMO to the nearest point on the ILM, rather than on the horizontal reference plane. It is the BMO-MRW and is defined as the minimum distance between the BMO and ILM in the ONH.Purpose:In this video, anatomy of the ONH and GMPE is decoded from a neophyte user’s point of view, as to why BMO-MRW is more important than the traditional BMO-HRW for glaucoma evaluation.Synopsis:The GMPE concepts are depicted in a novel dynamic (Clinical vs OCT Vs Histology) screenplay, detailing the below focal points with 2D & 3D animations: True Margin of ONH, Bruch’s Membrane (BM), Histology Vs OCT, BMO, Bruch’s Membrane Opening-Minimum Rim Width, Bruch’s Membrane Opening-Minimum Rim Width Versus Bruch’s Membrane Opening-Horizontal Rim Width, Alpha, Beta, Gamma Zone of ONH in OCT, Anatomic Positioning System, Impact of Fovea Bruch’s Membrane Opening Centre Axis.Highlights:This video also highlights, how with the advent of Anatomic Positioning System, scans were able to align relative to the individual’s Fovea-to-BMO-center (FoBMOC) axis at every follow-up, for accurately detecting changes, as small as 1 micron in BMO-MRW, thus creating a new world in diagnosing glaucoma and detecting glaucomatous progression with precision.Video link: https://youtu.be/6RqF5guAziw     

The current role of daily serum estriol monitoring in the insulin-dependent pregnant diabetic woman

This retrospective analysis of the use of serum estriol levels for antenatal assessment was performed in an effort to determine if routine, late third-trimester, daily serum estriol monitoring of insulin-dependent pregnant diabetic women can still be justified. Estriol profiles of 170 diabetic pregnancies, managed under a consistent protocol of weekly contraction stress tests and daily serum estriol assessments, were reviewed. A total of 4612 estriol determinations were performed. Nearly 4% of the estriol determinations showed a 35% fall from the mean of the previous three highest consecutive values. Forty-seven percent of the patients had at least one fall of this magnitude. Eighty-five percent of the fetal heart rate tests performed in association with an estriol fall were normal. A fall in estriol was not found to be associated with a higher risk of having a positive contraction stress test, either at the time the estriol fall was recognized or at any time during the patient's antepartum course. Although use of this strict protocol combining the use of weekly contraction stress tests and daily serum estriol determinations provided a safe method of antepartum assessment, there is little evidence to support the routine use of daily serum estriol monitoring in insulin-dependent pregnant diabetic women.     

Pandora's box: ethics of PGD for inherited risk of late-onset disorders

Until recently, the primary use of preimplantation genetic diagnosis (PGD) has been the selection of embryos to avoid lethal or debilitating gene mutations or abnormal chromosome complement. PGD can be used to reduce the risk of transferring to the uterus an embryo with Down syndrome, and parents who are carriers of severe genetic diseases may choose to avoid having children with these debilitating genetic conditions. The use of PGD is now being extended to include gene mutations that increase the risk of late-onset disorders such as breast and ovarian cancer. This paper argues for caution in advocating reproductive methods that are costly, have a limited chance of success, and for which the long-term outcome is unknown. Counselling should allow women a true choice of declining the option of PGD without recrimination, feelings of guilt or social pressure. There is concern that the Human Fertilisation and Embryology Authority has approved extension of PGD to late-onset multifactorial diseases without clear guidelines for its use. Guidelines for embryo selection should be revised to deal with potential conflict between reproductive success and genetic screening for disorders that do not profoundly affect the embryo or the children.     

Ethical considerations of fetal therapy

Fetal therapy raises ethical concerns in relation to the balance of potential benefit and harm, autonomy and informed consent, and the duties of the clinician to the pregnant women and fetus. Invasive therapy should be recommended only when it has a realistic chance of saving the life of the fetus and offspring or preventing serious and irreversible disease or disability. Clinicians should respect maternal choice and assessment of risk, particularly if the therapy might be only partially successful, leaving the offspring with a profound morbidity. Fetal therapy should not be undertaken without maternal consent; nor should it be presented coercively as an option to avoid a termination of pregnancy. Therapeutic procedures of unproven efficacy should be undertaken only with the voluntary informed consent of the pregnant woman and according to a clearly defined research protocol that has been approved by an appropriate research ethics committee and where appropriate support and counselling can be provided.     

THE EFFECT OF DIGITALIS ON THE NORMAL HUMAN ELECTROCARDIOGRAM,WITH ESPECIAL REFERENCE TO A-V CONDUCTION

Digitalis was given by mouth to five normal young male adults in amounts ranging from 2.0 to 3.0 gm. of standardized leaves in the course of 7 to 10 days. The As-Vs interval was prolonged in four of the five subjects, the greatest prolongation occurring in the case of the subject who received the most digitalis and none at all in one who received only 2.0 gm. There was no prolongation to so great an interval as 0.2 second until 2.7 gm. had been taken. The effects of the digitalis on conduction time began 5 to 6 days after the drug had been started and after 1.5 to 1.8 gm. had been taken. The effects persisted for 1 to 2 weeks after the drug had been stopped. Atropine removed completely the effect of digitalis on A-V conduction. The slowing heart rate after exercise was accompanied by an enhancement of the defect in conduction. The change in conduction through digitalis was therefore almost entirely, if not entirely, due to increase of vagal tone and irritability. Digitalis did not affect to an appreciable extent the Q-end of S and the Q-end of T intervals. Exercise and atropine both shortened the ventricular complex Q-end of T while the subject was under digitalis. The amplitude of the T wave, especially in Lead II, was changed within 48 hours after digitalis had been started, a decrease then beginning which became greater as the drug was continued and which persisted until 10 to 19 days after the digitalis had been stopped. The change in the T deflection preceded by several days the change in conduction time. The T wave, therefore, in the normal subject as well as in the patient gives us the earliest indication of digitalis action. The amplitudes of P, Q, R, and S were not materially influenced by the amounts of digitalis given. The pulse rate in two subjects became lower than usual at night as the result of the digitalis; otherwise there was no evidence of vagal action on the sino-auricular node. Blood pressure was uninfluenced by the digitalis. Mild subjective sensations occurred in all the subjects during the administration of the drug. A curious, hitherto undescribed, digitalis arrhythmia consisting of blocked auricular premature beats occurred in one subject after 3.0 gm. of digitalis had been taken.     

Repeated exposure to heterologous hepatitis C viruses associates with enhanced neutralizing antibody breadth and potency

A prophylactic hepatitis C virus (HCV) vaccine that elicits neutralizing antibodies could be key to HCV eradication. However, the genetic and antigenic properties of HCV envelope (E1E2) proteins capable of inducing anti-HCV broadly neutralizing antibodies (bNAbs) in humans have not been defined. Here, we investigated the development of bNAbs in longitudinal plasma of HCV-infected persons with persistent infection or spontaneous clearance of multiple reinfections. By measuring plasma antibody neutralization of a heterologous virus panel, we found that the breadth and potency of the antibody response increased upon exposure to multiple genetically distinct infections and with longer duration of viremia. Greater genetic divergence between infecting strains was not associated with enhanced neutralizing breadth. Rather, repeated exposure to antigenically related, antibody-sensitive E1E2s was associated with potent bNAb induction. These data reveal that a prime-boost vaccine strategy with genetically distinct, antibody-sensitive viruses is a promising approach to inducing potent bNAbs in humans.