[Recent eye surgery]. / Nouveautés en chirurgie oculaire.

The evolution of eye surgery has been truly extraordinary since the last decades, with the development of machines and techniques more and more accurate and effective. In this article will be detailed the novelties in terms of cataract surgery and refractive surgery.

L'évolution de la chirurgie oculaire a été vraiment extraordinaire depuis les dernières décennies, avec le développement de machines et techniques de plus en plus précises et efficaces. Dans cet article seront détaillées les nouveautés en termes de chirurgie de cataracte et chirurgie réfractive.

[Diagnosis of a sudden loss of vision (without redness nor eye pain)]. / Le diagnostic d'une perte de vue brutale (sans rougeur ni douleur oculaire).

Sudden loss of vision without redness nor eye pain may come from numerous causes of varying severity. It presents a major source of anxiety for the patient who will seek for urgent consultation. The diagnostic approach is based on history and eye examination, eventually completed by a neurological examination. The purpose of this article is to provide general practitioners simple clues allowing them to quickly orientate the diagnosis. Following simple guidelines, they will be able to treat the condition correctly or refer to an adequate specialist when needed. True emergencies are retinal detachment, central retinal artery occlusion, intracranial hypertension, Horton giant cells arteritis, transient ischemic attack, stroke, pituitary apoplexy and cortical visual loss.

Giant cell arteritis: the internist should not be a lone rider in this potentially blinding condition.

We report the case of a 66-year-old woman with visual loss due to anterior ischaemic optic neuropathy. The diagnosis of giant cell arteritis was made on the basis of classic clinical characteristics and haematological abnormalities. Despite corticosteroid treatment, involvement of the other eye occured, resulting in a bilateral and permanent loss of vision. The follow-up was marked by two relapses within the 6 months after the first episode. In order to prevent blindness, ophthalmologists should be familiar with this disorder and should actively participate in the treatment, not leaving the internist deciding alone about tapering corticotherapy.

Congenital stationary night blindness in a patient with mild learning disability due to a compound heterozygous microdeletion of 15q13 and a missense mutation in TRPM1.

The complete form of congenital stationary night blindness (cCSNB) represents a non-progressive retinal disorder characterized by night vision problems and often congenital nystagmus, reduced vision, high myopia, strabismus and normal fundus appearance. Clinically this form of CSNB can be diagnosed by full-field electroretinogram. The mode of inheritance can be X-linked and autosomal recessive with mutations in genes coding for proteins mainly present at the dendritic tips of ON-bipolar cells. Mutations in NYX, GRM6, GPR179, LRIT3 and TRPM1 lead to this condition. The latter gene defect represents the major form underlying cCSNBC. It codes for the melastatin-related transient receptor 1 expressed in the inner nuclear layer of the retina, with the protein localized in ON-bipolar cells. To date, various homozygous or compound heterozygous mutations in TRPM1 have been reported. Small chromosomal rearrangements are frequent cause of mental retardation. In rare cases deletions can overlap with a mutation on the remaining chromosome and lead to a recessive disorder. Here, we describe a patient with mild neurological deficiencies and cCSNB caused by a microdeletion on 15q32 overlapping with a TRPM1 variant.

A proof-of-concept study of the effectiveness of a removable device for offloading in patients with neuropathic ulceration of the foot: the Ransart boot.

AIM: To undertake a proof-of-concept study to determine whether a removable offloading device (the Ransart boot) for the management of diabetic foot ulcers (DFU) was as effective as reports of non-removable devices. RESEARCH DESIGN AND METHODS: This observational study used the Ransart boot for patients with DFU, in seven specialist centres. If a patient had two or more ulcers, one was selected as the index ulcer. Ulcers were classified by the University of Texas (UT) system. RESULTS: There were 135 patients (mean age 60.3 +/- 11.4 years); 96 (71.1%) male. Median ulcer duration at presentation was 90 [interquartile range (IQR) 30-1825] days. Seven were lost to follow-up, seven developed other major illnesses and four died; outcomes were documented in the remaining 117. Eighty-two (70.1% of 117) healed, after a median (IQR) 60 (43-99) days, while 22 (18.8%) ulcers were resolved by amputation (one major). The remaining 13 (11.1%) patients were judged non-compliant. There was a close correlation between ulcer classification at baseline and both time to healing (P < 0.001 chi(2)-test) and amputation (P < 0.001; Spearman's rank correlation coefficient). There was a positive correlation between ulcer duration at presentation and time to healing (P < 0.02), UT class (P < 0.01), glycated haemoglobin (P < 0.02) and amputation (P < 0.04). CONCLUSIONS: Time to healing and incidence of amputation were comparable with those previously reported for non-removable devices. Given that a removable device is much more acceptable to the patient, the effectiveness, cost and acceptability of the removable devices, such as the Ransart boot, need to be compared with a non-removable device in a randomized trial. Diabet. Med. 26, 778-782 (2009).

Fundus autofluorescence in a case of occult macular dystrophy.

PURPOSE: To document for the first time intrinsic retinal pigment epithelium (RPE) fluorescence in occult macular dystrophy (OMD). This entity is characterized by a central cone dysfunction leading to a decline of visual acuity without visible fundus and fluorescein angiography abnormalities. A great variability in clinical findings and in the pattern of inheritance have been reported suggesting probably several etiologies of which some are well known but seen too early to detect significant changes. METHODS: Fundus autofluorescence imaging is a recent method to detect early retinal pigment epithelial alterations. It may visualise disease specific abnormalities in the retinal pigment epithelium often not yet visible on ophthalmoscopy such as Stargardt disease, rod-cone dystrophy. This method was applied in a member of a family with OMD. RESULTS: The normal fundus autofluorescence observed in our patient allowed the distinction between well-known maculopathies not yet visible on ophthalmoscopy but showing abnormal autofluorescence, and genuine occult macular dystrophy. CONCLUSION: Fundus autofluorescence imaging in our case of dominant autosomal OMD suggests a healthy and functional RPE. This examination of RPE should therefore be added to the work-up of suspected OMD.

Actin filaments and myosin I alpha cooperate with microtubules for the movement of lysosomes.

An earlier report suggested that actin and myosin I alpha (MMIalpha), a myosin associated with endosomes and lysosomes, were involved in the delivery of internalized molecules to lysosomes. To determine whether actin and MMIalpha were involved in the movement of lysosomes, we analyzed by time-lapse video microscopy the dynamic of lysosomes in living mouse hepatoma cells (BWTG3 cells), producing green fluorescent protein actin or a nonfunctional domain of MMIalpha. In GFP-actin cells, lysosomes displayed a combination of rapid long-range directional movements dependent on microtubules, short random movements, and pauses, sometimes on actin filaments. We showed that the inhibition of the dynamics of actin filaments by cytochalasin D increased pauses of lysosomes on actin structures, while depolymerization of actin filaments using latrunculin A increased the mobility of lysosomes but impaired the directionality of their long-range movements. The production of a nonfunctional domain of MMIalpha impaired the intracellular distribution of lysosomes and the directionality of their long-range movements. Altogether, our observations indicate for the first time that both actin filaments and MMIalpha contribute to the movement of lysosomes in cooperation with microtubules and their associated molecular motors.

Association of myosin I alpha with endosomes and lysosomes in mammalian cells.

Myosin Is, which constitute a ubiquitous monomeric subclass of myosins with actin-based motor properties, are associated with plasma membrane and intracellular vesicles. Myosin Is have been proposed as key players for membrane trafficking in endocytosis or exocytosis. In the present paper we provide biochemical and immunoelectron microscopic evidence indicating that a pool of myosin I alpha (MMIalpha) is associated with endosomes and lysosomes. We show that the overproduction of MMIalpha or the production of nonfunctional truncated MMIalpha affects the distribution of the endocytic compartments. We also show that truncated brush border myosin I proteins, myosin Is that share 78% homology with MMIalpha, promote the dissociation of MMIalpha from vesicular membranes derived from endocytic compartments. The analysis at the ultrastructural level of cells producing these brush border myosin I truncated proteins shows that the delivery of the fluid phase markers from endosomes to lysosomes is impaired. MMIalpha might therefore be involved in membrane trafficking occurring between endosomes and lysosomes.

[Classification and profile of adverse drug effects]. / Classification et profils des effetS secondaires médicamenteux.

It is necessary to classify adverse drug reactions by grading the certainty of causal relationship between the drug administration and the adverse reaction. The most widely used classification is the one of the World Health Organization (WHO).

[Visual cortes--is it a concern?]. / Le cortex visuel est-il concerné?

The visual cortex may be involved in adverse drug reactions, leading to three different clinical presentations: cortical blindness, visual hallucinations and visual aura without headache. The drugs with potential visual cortex toxicity are described.

[Toxicity of recent and less recent drugs on the optic nerve. Does Viagra cause blindness?]. / Toxicité des médicaments récents et moins récents sur le nerf optique. Le Viagra rend-il aveugle?

The optic nerve is quite vulnerable to the toxic effect of drugs. Since the last thirty years new drugs have appeared that are potentially harmful to the optic nerve. They are described.

Excision of 8-oxoguanine within clustered damage by the yeast OGG1 protein.

Clustered damages are formed in DNA by ionising radiation and radiomimetic anticancer agents and are thought to be biologically severe. 7,8-dihydro-8-oxoguanine (8-oxoG), a major DNA damage resulting from oxidative attack, is highly mutagenic leading to a high level of G.C-->T.A transversions if not previously excised by OGG1 DNA glycosylase/AP lyase proteins in eukaryotes. However, 8-oxoG within clustered DNA damage may present a challenge to the repair machinery of the cell. The ability of yeast OGG1 to excise 8-oxoG was determined when another type of damage [dihydrothymine, uracil, 8-oxoG, abasic (AP) site or various types of single-strand breaks (SSBs)] is present on the complementary strand 1, 3 or 5 bases 5' or 3' opposite to 8-oxoG. Base damages have little or no influence on the excision of 8-oxoG by yeast OGG1 (yOGG1) whereas an AP site has a strong inhibitory effect. Various types of SSBs, obtained using either oligonucleotides with 3'- and 5'-phosphate termini around a gap or through conversion of an AP site with either endonuclease III or human AP endonuclease 1, strongly inhibit excision of 8-oxoG by yOGG1. Therefore, this large inhibitory effect of an AP site or a SSB may minimise the probability of formation of a double-strand break in the processing of 8-oxoG within clustered damages.

Activation of p65 NF-kappaB protein by p210BCR-ABL in a myeloid cell line (P210BCR-ABL activates p65 NF-kappaB).

The chimeric tyrosine kinase p210BCR-ABL is involved in the pathogenesis of chronic myelogenous leukemia. It transforms immature hematopoietic cells in vitro and abrogates IL-3-dependent growth. The mechanisms by which p210BCR-ABL mediates its oncogenicity are not well elucidated. Identifying transcription factors targeted by the chimeric protein may help to clarify these mechanisms. We have analysed the effect of p210BCR-ABL expression on NF-kappaB activity in DA1 cells (an IL-3-dependent murine myeloid progenitor cell line). A specific stimulation of NF-kappaB activity by kinase-active wild-type p210BCR-ABL has been evidenced by transcriptional activation assays. Electrophoretic mobility supershift assays revealed the presence of p65 protein (RelA) DNA binding activity in p210BCR-ABL transformed DA1 cells but not in parental DA1 cells. Activation of RelA in transformed DA1 cells may occur by protein stabilization. Experiments using oligonucleotides antisense to RelA showed that p210BCR-ABL transfected cells failed to survive after IL-3 removal. Moreover, inhibition of cellular growth was shown following treatment of p210BCR-ABL transformed DA1 cells by p65 antisense oligonucleotides. This study suggests that p65 NF-kappaB may be an effector for p210BCR-ABL and probably contributes to its induced transformation process.

c-Myb protein binds to the EP element of the HBV enhancer and regulates transcription in synergy with NF-M.

The hepatitis B virus (HBV) enhancer contains multiple active elements, one of which is the EP element, a 15 bp site important for its regulation by acting on other functional elements like the E site. The EP element, in the HBV enhancer context, contains two putative binding sites for c-myb family gene products. Electrophoretic mobility shift assays showed that the minimal c-Myb DNA-binding domain binds to the EP sequence. DNase I footprinting experiments revealed that only one consensus binding site was effectively protected. We found that c-Myb down-regulates transcription driving by the HBV enhancer in CAT assays performed in a haematopoietic (K562) and in a hepatic (HepG2) cell line. Interestingly, co-expression of both c-Myb and NF-M, a C/EBPbeta homologue which recognises the E element of the HBV enhancer, showed a synergistic transactivation of the HBV enhancer while, separately, each of them had an inhibitory effect on transcription in HepG2 and K562 cell lines, two cell types potentially infected by the hepatitis B virus.

Screening for amblyogenic factors in preschool children with the retinomax hand-held refractor: do positive children have amblyopia and is treatment efficacious?

PURPOSE: To determine the visual acuity (VA) in a group of preschool children who were true positives for refractive screening (positive group) in order to compare it with the VA of a sample of children without any refractive anomaly (control group); also, to investigate if true-positive treated children can achieve the VA of the control group within what delay. METHODS: Fifty seven children without any refractive anomaly were tested with the VA child chart if the Nidek SCP 670 projector; 47 children presenting with the refractive anomalies were tested with the same chart. A Kruskal Wallis exact test for singly ordered tables were used to compare VA between those groups and a non-parametric Wilcoxon test for paired samples was used to compare pre- and post-treatment VA in 27 children of the positive group. The mean time necessary to achieve the post-treatment VA was calculated. RESULTS: Median VA: 20/20 in the control group, 20/33 in the positive group. The VA difference between the two pre- and post-treatment VA are highly significant. Among the 27 treated children, pre-treatment median VA was 20/50, post-treatment 20/20. The differences between the pre- and post-treatment VA was 9 months. CONCLUSION: The positive group had a significantly lower VA than the control group. In the treated group, treatment initiated at a mean age of 4 years resulted in an increase in VA to that of the control group after an average time of 9 months, encouraging early screening and treatment before VA is measureable in order to shorten this delay.

Magnetic enzyme membranes as active elements of electrochemical sensors. Lactose, saccharose, maltose bienzyme electrodes.

The direct monitoring of sugars such as lactose, maltose, saccharose is not only useful at the applied point of view but also at the fundamental point of view for studying enzymology, especially in microbiology and fermentation. Benzyme systems were extensively used in solution for analytical applications in industry and medicine. The progress in the field of immobilization of bienzyme systems [1-3], especially within membranes [4-5], makes possible the production of new analytical devices. From the studies dealing with concentration profiles in artificial enzyme membranes [14], evidence was obtained for a well defined relationship between the local concentration of a metabolite and concentration of the first substrate in the bulk solution. In the described systems a substrate is transformed into glucose within a membrane, the glucose is then transformed in gluconic acid with a local oxygen consumption. The local pO2 level is linked to the glucose oxidase velocity, which is only linked to the glucose production, that is to say to the concentration of the first substrate. The enzyme electrode is based on the transformation of kinetic phenomena (reaction rates) into absolute values (local concentrations) through the diffusion-reaction coupling process. The manufacture of magnetic enzyme electrodes [6] allows convenient use of the active sensors. The pO2 electrode has some adventages, namely the specificity based on the selectivity of the gas permeable membrane and the linear relationship between the oxygen and the output of the electrode. pCO2, pH, ion electrodes give a logarithmic response as a function of the concentration. The grafting of a multienzyme system on a sensor allows a study of sequential systems in a defined context with a measurement of the local concentration of the metabolites. The tool is useful for both kinetics [4] and regulation studies [5].

Determination of the human c-Abl consensus DNA binding site.

c-Abl tyrosine kinase, an essential protein of the cell cycle signalling pathways, is implicated in the regulation of RNA polymerase II activity, apoptosis and DNA repair. Its DNA binding activity is important for its biological functions. However, the molecular basis of c-Abl interaction with DNA remains largely unclear. We delimited the human c-Abl DNA binding domain and identified its preferred binding site, 5'-A(A/C)AACAA(A/C). The central AAC motif is highly conserved and constitutes the major core element in the binding sites. EMSAs and footprinting experiments were performed to explore how the c-Abl fusion protein recognizes specific sequences in DNA.