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Biomedical subjects

D Benezra

Publications and source records attributed to D Benezra.

At least 19 recordsLinked to original sources
PubMed2006

Krypton laser photocoagulation induces retinal vascular remodeling rather than choroidal neovascularization.

The purpose of this study is to analyze the retina and choroid response following krypton laser photocoagulation. Ninety-two C57BL6/Sev129 and 32 C57BL/6J, 5-6-week-old mice received one single krypton (630 nm) laser lesion: 50 microm, 0.05 s, 400 mW. On the following day, every day thereafter for 1 week and every 2-3 days for the following 3 weeks, serial sections throughout the lesion were systematically collected and studied. Immunohistology using specific markers or antibodies for glial fibrillary acidic protein (GFAP) (astrocytes, glia and Muller's cells), von Willebrand (vW) (vascular endothelial cells), TUNEL (cells undergoing caspase dependent apoptosis), PCNA (proliferating cell nuclear antigen) p36, CD4 and F4/80 (infiltrating inflammatory and T cells), DAPI (cell nuclei) and routine histology were carried out. Laser confocal microscopy was also performed on flat mounts. Temporal and spatial observations of the created photocoagulation lesions demonstrate that, after a few hours, activated glial cells within the retinal path of the laser beam express GFAP. After 48 h, GFAP-positive staining was also detected within the choroid lesion center. "Movement" of this GFAP-positive expression towards the lasered choroid was preceded by a well-demarcated and localized apoptosis of the retina outer nuclear layer cells within the laser beam path. Later, death of retinal outer nuclear cells and layer thinning at this site was followed by evagination of the inner nuclear retinal layer. Funneling of the entire inner nuclear and the thinned outer nuclear layers into the choroid lesion center was accompanied by "dragging" of the retinal capillaries. Thus, from days 10 to 14 after krypton laser photocoagulation onward, well-formed blood capillaries (of retinal origin) were observed within the lesion. Only a few of the vW-positive capillary endothelial cells stained also for PCNA p36. In the choroid, dilatation of the vascular bed occurred at the vicinity of the photocoagulation site and around it. Confocal microscopy demonstrates that the vessels throughout the path lesion are located within the neuroretina while in the choroid (after separation of the neural retina) only GFAP-positive but no lectin-positive cells can be seen. The involvement of infiltrating inflammatory cells in these remodeling and healing processes remained minimal throughout the study period. During the 4 weeks following krypton laser photocoagulation in the mouse eye, processes of wound healing and remodeling appear to be driven by cells (and vessels) originating from the retina.

Animals↗
PubMed2003

Delivery of antisense oligonucleotide to the cornea by iontophoresis.

We wished to evaluate the potential of iontophoresis to promote the delivery of antisense oligonucleotides (ODN) directed at the vascular endothelial growth factor (VEGF)-R2 receptor (KDR/Flk) to the cornea of the rat eye. Fluorescence (CY5)-labeled ODNs in phosphate-buffered saline (PBS) (20 microM) were locally administered to rat eyes, and their fate within the anterior segment was studied. Thirty-four male, 5-week-old Wistar rats were used for all experiments. The rats were divided in four groups. In group I (12 rats, 12 eyes), the ODNs (20 microM) were delivered by iontophoresis (300 microA for 5 minutes) using a specially designed corneal applicator. In group II (12 rats, 12 eyes), the ODNs (20 microM) were delivered using the same applicator, but no electrical current was applied. In group III (6 rats, 6 eyes), a corneal neovascular reaction was induced prior to the application of ODNs (20 microM), and iontophoresis electrical current was delivered as for group I rats. Group IV (4 rats, 4 eyes) received ODN (60 microM) iontophoresis application (300 microA for 5 minutes) and were used for ODN integrity studies. The animals were killed 5 minutes, 90 minutes, and 24 hours after a single ODN application and studied. Topically applied ODNs using the same iontophoresis applicator but without current do not penetrate the cornea and remain confined to the superficial epithelial layer. ODNs delivered with transcorneoscleral iontophoresis penetrate into all corneal layers and are also detected in the iris. In corneas with neovascularization, ODNs were particularly localized within the vascular endothelial cells of the stroma. ODNs extracted from eye tissues 24 hours after iontophoresis remained unaltered. The iontophoresis current did not cause any detectable ocular damage under these conditions. Iontophoresis promotes the delivery of ODNs to the anterior segment of the eye, including all corneal layers. Iontophoresis of ODNs directed at VEGF-R2 may be used for the design of specific antiangiogenic strategy in diseases of the cornea.

Animals↗
PubMed2001

Patterns of intraocular inflammation in children.

AIM: To report on the causes of uveitis in children and young adults and their effects on visual functions. MATERIALS AND METHODS: Two hundred and seventy six patients, 18 years old or younger, with uveitis were included in this study. The intraocular inflammation (uveitis) was classified according to anatomical site of ocular involvement and the most probable etiological factor. The final diagnosis was based on clinical manifestations and the results of specific laboratory investigations. RESULTS: Bilateral intraocular inflammation was observed in 70.3% of the cases and 29.7% had either the left or the right eye involved. The symptomatology was relatively mild in most cases despite the fact that the visual acuity was markedly affected. An associated systemic disease was detected in 40.2% of the cases classified as non-infectious. Of this group, juvenile rheumatoid arthritis was the most common single systemic associated cause detected in 41 children. In 110 children (59.8%), the uveitis was strictly confined to the eyes with 70 of these (25.4% of the total group) classified as idiopathic. Parasites were the most common infectious-associated cause for the uveitis followed by viruses and bacteria. CONCLUSION: Uveitis is highly prevalent among children. In children, symptomatology of the intraocular inflammation may be very mild. However, visual acuity is markedly reduced leading to amblyopia in the young children. Early detection and treatment is therefore of utmost importance.

Adolescent↗
PubMed1997

Blood serum interleukin-1 receptor antagonist in pars planitis and ocular Behçet disease.

PURPOSE: To determine the levels of interleukin-1 receptor antagonist (IL-1ra) in the blood serum of patients with idiopathic bilateral pars planitis and Behçet disease. METHODS: Five milliliters of blood was with-drawn from the cubital vein of 91 patients (58 with the ocular type and five with the combined type of Behçet disease; 28 with pars planitis) and 36 volunteers. Serum was separated from these samples and stored at -70 C until assayed. Interleukin-1 receptor antagonist levels were determined by human IL-1ra enzyme-linked immunosorbent assay kits. In patients not receiving any systemic medication, one serum sample was obtained before initiating treatment and another when the patients had been under full medical treatment for 6 weeks or more. RESULTS: Pretreatment mean +/- SD serum IL-1ra levels were 320 +/- 32 pg/ml for the patients with pars planitis, 380 +/- 54 pg/ml for patients with Behçet disease, and 271 +/- 29 pg/ml for the control subjects (no statistical significance). During treatment, a mean serum level of 352 +/- 37 pg/ml was observed in patients with pars planitis (not significantly different from control subjects) and 538 +/- 79 pg/ml in patients with ocular Behçet disease (P = .0116 compared with control subjects). The greatest increase in IL-1ra levels was observed in patients with Behçet disease who received a combination of cyclosporine and corticosteroids. CONCLUSIONS: Because IL-1ra is one of the natural immunomodulating molecules, the significant increase of serum IL-1ra levels, especially after combined treatment with cyclosporine and corticosteroids, could indicate that the therapeutic effects of this regimen may be mediated through its effects on this molecule.

Behcet Syndrome↗
PubMed1991

[Injection of botulinum toxin into the oculomotor muscles in disorders of ocular motility].

Injections of botulinum toxin into the oculomotor muscles was used in incorrectible diplopia, ocular torticollis, Duane's syndrome and congenital nystagmus. Favourable results were obtained and the sole complications which could be observed were a transitory ptosis and subconjunctival haemorrhages. Frequently 2 to 3 injections were sufficient for a permanent effect.

Adolescent↗
PubMed1990

[Implantation of intraocular lenses in children].

Implantation of intraocular lenses in children was performed in 42 cases in our department. In 26 children it concerned primary implants, in 16 secondary implants. No major postoperative complications were observed in the period between the 6th and the 24th month after surgery. The visual acuity of 0.5 or better showed 70 p.c. of children after the primary and 66 p.c. after secondary implants.

Adolescent↗
PubMed1988

A larger spectrum of severe HIV-1--related disease in intravenous drug users in New York City.

Increasing mortality in intravenous (IV) drug users not reported to surveillance as acquired immunodeficiency syndrome (AIDS) has occurred in New York City coincident with the AIDS epidemic. From 1981 to 1986, narcotics-related deaths increased on average 32% per year from 492 in 1981 to 1996 in 1986. This increase included deaths from AIDS increasing from 0 to 905 and deaths from other causes, many of which were infectious diseases, increasing from 492 to 1091. Investigations of these deaths suggest a causal association with human immunodeficiency virus (HIV) infection. These deaths may represent a spectrum of HIV-related disease that has not been identified through AIDS surveillance and has resulted in a large underestimation of the impact of AIDS on IV drug users and blacks and Hispanics.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Prospective study of infections in indwelling central venous catheters using quantitative blood cultures.

PURPOSE: Surgically implanted central venous catheters are widely used in cancer patients in whom there is a need for prolonged venous access for chemotherapy, parenteral nutrition, antibiotics, and blood sampling. This study evaluated catheter infectious complications, including catheter-related sepsis, exit site infection, and tunnel infection. Specifically, an evaluation of the incidence, type, and response to treatment of indwelling catheter infections was performed, and conditions under which the catheter should be removed were delineated. PATIENTS AND METHODS: During the year of this study, 488 central venous catheters were implanted. Records were maintained on demographic variables, date of catheter implantation, surgeon, white blood cell count, absolute neutrophil count, and underlying diagnosis. Blood for both aerobic and anaerobic culture was collected from each patient. For patients in whom infection developed, clinical features, white blood cell count, absolute neutrophil count, and microbiologic data were noted, as were the clinical course and response to treatment. RESULTS: A total of 142 episodes of infectious complications were documented. There were 88 episodes of catheter-related sepsis, and 33 of 54 evaluable episodes (61 percent) were successfully treated with antibiotics. There were 34 episodes of exit site infection, and 20 of the 29 evaluable episodes (69 percent) were successfully treated with antibiotics and local care. Of the 20 tunnel infections, only five (25 percent) were successfully treated with antibiotics, and the other 15 required catheter removal for cure. Twelve of the 15 cases requiring catheter removal were caused by Pseudomonas species. CONCLUSION: On the basis of these results, compulsory removal of the catheter is not required in cases of catheter-related sepsis. Similarly, exit site infections can often be cured by means of antibiotics and local care. However, catheter removal is required to achieve cure in most tunnel infections, particularly if Pseudomonas species are cultured from the exit sites of patients with tunnel infection.

Adult↗
PubMed1986

Treatment and visual prognosis in Behçet's disease.

For the last decade we have observed and regularly followed 49 patients with the ocular type of Behçet's disease. Thirty-six patients were males and 13 were females. Regardless of whether the initial ocular presenting symptoms were in the anterior or posterior segment, both segments were involved within two years. Sterile hypopyon was recorded in 17 out of the 49 patients during the process of follow-up. In three of the patients hypopyon was the presenting symptom. Characteristically there was a lack of corneal or scleral involvement in the disease process. All patients responded initially to treatment with steroids, but 42 had a course of treatment with cytotoxic-immunosuppressive drugs for various lengths of time after 'resistance' to steroids developed. Although definitely effective in reducing the intensity of the ocular inflammatory processes, it is not clear yet whether these modes of treatment have any dramatic effect of the visual prognosis of the affected eyes. Despite intensive follow-up and treatment, loss of useful visual acuity has occurred in 74% of the eyes six to 10 years after the start of the ocular symptoms.

Azathioprine↗
PubMed1985

Anti-retinal auto-antibodies in Vogt-Koyanagi-Harada syndrome, Behcet's disease, and sympathetic ophthalmia.

Sera of patients diagnosed as having the active Vogt-Koyanagi-Harada (VKH) syndrome, Behcet's syndrome or sympathetic ophthalmia as well as normal controls were evaluated by ELISA and by staining of normal human retinal tissue using the avidin-biotin-peroxidase complex (ABC) technique for anti-retinal antibodies. No anti-retinal S-antigen antibodies were detected by ELISA. However, autoimmune antibodies were found against the outer segments of photoreceptors and Müller cells in patients with the VKH syndrome, with lower titers in some patients with Behcet's syndrome, and in a few patients with sympathetic ophthalmia. These results suggested anti-retinal antibodies were present and that retinal autoimmunity may play a role in pathogenesis in varieties of posterior uveitis. In addition, the indirect immunoperoxidase staining technique may facilitate the diagnosis of VKH in uncertain cases.

Autoantibodies↗
PubMed1985

Immunohistochemistry and electron microscopy of choroidal infiltrates and Dalen-Fuchs nodules in sympathetic ophthalmia.

An immunohistological study using monoclonal antibodies directed at specific membrane antigens of various inflammatory cells was carried out in order to evaluate the identity and topographic localization of the immuno-competent cells in an enucleated eye from a 6-year-old black patient with a three-month history of sympathetic ophthalmia. Correlative light and transmission electron microscopic examination of serial sections was also performed. The data demonstrated that the predominant cells within the choroidal infiltrate were T-lymphocytes (Leu 1+). T-cell subset analysis disclosed that most of these cells harbored specific antigenic determinants of the helper phenotype (Leu 3a+). A smaller proportion of the T cells demonstrated the specific determinants of the suppressor subtype (Leu 2a+). The helper/suppressor ratio varied slightly and ranged in most areas of the choroid between 3:1 and 4:1. Additionally, approximately 15% of the infiltrating lymphocytes harbored the Leu 14+ determinant specific for B cells. The latter were located in the outer choroid adjacent to the sclera. Very few natural killer (NK) cells (Leu 7+) were identified throughout the choroid. The granulomatous foci in the choroid were composed mainly of epithelioid cells and histiocytes expressing the OKM1+ and M221+ antigenic determinants on their membranes and demonstrating a high cytoplasmic nonspecific esterase activity (ANAE+). Within the Dalen-Fuchs nodules, similar to the choroidal nodules, there was a predominance of histiocytes and epithelioid cells (OKM1+, M221+, ANAE+), a few T-helper cells (Leu 1+, Leu3a+) and some OKM1-, M221- cells whose origin could not be determined. These findings were corroborated by electron microscopic observations of serial sections. Careful light and electron microscopic studies disclosed breaks in Bruch's membrane underlying some of Dalen-Fuchs nodules. In our opinion, these observations may be interpreted as the demonstration that Dalen-Fuchs' nodules and the choroidal granulomatous foci could be formed by identical cells of similar function and origin.

Child↗
PubMed1985

Bilateral optic nerve abnormalities associated with a 4-10 chromosomal translocation.

A neonate with ocular abnormalities and a chromosomal aberration is described. The patient demonstrates a typical choroidal coloboma involving the iris ciliary body and choroid of the right eye, bilateral optic pits-coloboma and a karyotype with a 4-10 chromosomal translocation. Although a random occurrence of the ocular phenomena and the chromosomal aberration cannot be ruled out, it is appealing to speculate about the possible association of the ocular colobomata and the chromosomal translocation harbored by this patient.

Choroid↗