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Biomedical subjects

C Baudouin

Publications and source records attributed to C Baudouin.

At least 127 records · Page 7Linked to original sources
PubMed1996

Side effects of antiglaucomatous drugs on the ocular surface.

An increasing number of studies, both experimental and epidemiologic, have shown that filtering glaucoma surgery has progressively become less effective than initially described. Of a number of risk factors for failure, duration and number of antiglaucoma drugs before surgery seem to play a critical role, and high accumulated antiglaucoma topical treatments significantly reduce success rates. Histopathologic studies have confirmed that topically applied drugs may exert toxic effects to the corneoconjunctival surface and induce chronic infraclinical inflammation, as shown by the presence of immunologic changes and inflammatory infiltrates in multitreated eyes. The origin of topical inflammation has not yet been clearly determined, but benzalkonium chloride, which is used as a preservative in almost all antiglaucoma preparations, has shown strong evidence of toxicity to the ocular surface. A number of questions remain to be investigated, but suppression of preservatives from chronically applied drugs should be a critical issue in the near future.

Adrenergic beta-Antagonists↗
PubMed1996

Treatment of cytomegalovirus retinitis in AIDS patients using intravitreal injections of highly concentrated ganciclovir.

PURPOSE: Intravitreal injections of ganciclovir provide a useful adjunct or alternative treatment for cytomegalovirus retinitis in AIDS patients when toxicity or progression is seen with systemic administration of antiviral drugs. To avoid transient increase in intraocular pressure that may impair optic nerve vascularization in long-term treated patients, we modified conventional procedures by injecting a smaller volume of a more concentrated ganciclovir solution. PATIENTS AND METHODS: We used intravitreal injections of 350 micrograms of ganciclovir in a final volume of 50 microliters, in 156 eyes from 111 AIDS patients, 14-53 years old, presenting with necrotizing retinitis despite systemic antiviral agents or who had become intolerant to systemic treatment. RESULTS: Patients underwent a total of 2,890 injections. The mean number of injections was 25.9 +/- 3.2 by patient, with a maximal duration of 32 months (with a total of 220 injections in 1 patient). Forty-five of the 111 patients received bilateral intravitreal injections, 8 had more than 80 injections each. The only major complications were 4 cases of endophthalmitis causing a total loss of vision in 2 eyes, 1 retinal detachment and 3 cases of slow progression of retinitis resulting in optic nerve atrophy despite treatment. We observed a very low rate of amaurosis and ocular pain. Relapse occurred after 2-3 weeks whenever treatment was stopped, so that intravitreal ganciclovir was not discontinued until the patient's death or reintroduction of systemic treatment. CONCLUSIONS: This procedure confirmed the good efficacy of intravitreal ganciclovir in halting progression of retinitis. Injection of a smaller volume of ganciclovir reduced repeated amaurosis and ocular pain. It was considered by patients as improving their comfort and quality of life, thus increasing their compliance to treatment and reducing side effects as compared to usual protocols.

AIDS-Related Opportunistic Infections↗
PubMed1996

[Immunophenotype of dendritic cells of the human conjunctiva].

PURPOSE: To examine dendritic cells from human conjunctiva and to characterize their surface markers immunologically. METHODS: Conjunctival cells were isolated by conjunctival impression cytology from 150 patients: controls (65 patients, 126 eyes) or with various chronic inflammatory conditions (85 patients, 160 eyes); and by conjunctival biopsies from 25 patients: controls (10 patients) or treated topically for primary open angle glaucoma (15 patients). Immunostaining was performed using antibodies to investigate expression of 21 different membrane markers relevant to immunologic functions of dendritic cells. RESULTS: Conjunctival dendritic cells exhibited surface markers both in normal and inflammatory conditions: class II antigens HLA-DR and HLA-DQ, CD1a, vimentin, CD11a and CD18 (LFA-1), CD22, CD45RO and CD50. Some markers were more occasionally found CD4, CD11b, CD29, CD32, CD45RA and CD54, others being almost totally absent. Conjunctival inflammation induced the migration of dendritic cells from the stroma to the epithelium and thus increased their density. CONCLUSION: We conclude that conjunctival dendritic cells show common immunophenotypic features with those of other nonlymphoid tissues. Thus, conjunctival dendritic cells may be important in the immune regulation of the anterior segment.

Adult↗
PubMed1996

[Stages of cell proliferation in an experimental model of vitreoretinal proliferation following injection of platelet-rich plasma].

PURPOSE: To understand the pathophysiogenesis of the proliferative retinopathies, with a simple and valuable tool, for pathophysiologic and therapeutic assays. METHODS: We prepared a 10 million platelet concentrate from the same donor in 30 microliters, directly injected into the right eye of 46 pigmented and 14 albino rabbits. Animals were sacrificed at days 7, 14, 21 and one month after injection. Before histopathological analysis, all animals were followed clinically to evaluate the vitreoretinal proliferation, scored according to a 6 grade classification. RESULTS: Vitreoretinal proliferation started at day 5 or 8 after injection and increased during the 3 following weeks. Eighty per cent of the eyes showed at the end of the first month a tractional retinal detachment. histopathology revealed intense cell migration and proliferation close to ciliary body appearing from the 7th day, then further increasing rapidly. Immunostaining showed cell infiltrates expressing vimentin and cytokeratin. Overexpression of vimentin was also found in ciliary and retinal epithelia, and in Müller cells. CONCLUSION: This simple and valuable model can reproduce some characteristics of human vitreoretinal proliferations, such as the involvement of the ciliary body and the retinal pigment epithelium, inflammatory mechanisms occurring together with cell proliferation, and significant disturbances of cytoskeleton within deep ocular structures. Furthermore, this study is a first step on the way of antiproliferative assays, and for a better understanding of pathogenesis of intraocular proliferative disorders.

Animals↗
PubMed1996

Mechanisms of failure in glaucoma filtering surgery: a consequence of antiglaucomatous drugs?

An increasing number of studies, both experimental and epidemiologic, have provided evidence that filtering glaucoma surgery may be less effective than initially described. Of a number of risk factors for failure, duration and number of antiglaucoma drugs prior to surgery seem to play a critical role and highly accumulated antiglaucoma topical treatments significantly reduce success rates. Histopathological studies have confirmed that topically applied drugs may exert toxic effects to the corneoconjunctival surface, and induce chronic infraclinical inflammation, as shown by the presence of immune and inflammatory infiltrates in multitreated eyes. The origin of topical inflammation has not yet been clearly determined, but a common component of ophthalmic drugs, the benzalkonium chloride used as preservative in almost all antiglaucoma preparations, has shown strong evidence of toxicity. A number of questions remain to be investigated, but suppression of preservatives from chronically applied drugs should be a critical issue in the near future.

Animals↗
PubMed1995

Post partum magnetic resonance imaging: lumbar tissue changes are unrelated to epidural analgesia or mode of delivery.

Thirty five women consented post partum to daily lumbar back pain assessments and magnetic resonance imaging (MRI) (0.15 Tesla) within 48 hours of delivery using a T(1) weighted spin echo and a fat suppression sequence (STIR) to identify tissue water. Nine women (26%) had lumbar disc abnormalities on MRI scan. Variable degrees of soft tissue changes in the lumbar region were observed using the STIR sequence in all patients after delivery. Eight women (23%) had mild, 15 (43%) moderate, and 12 (34%) severe changes with an average of 5 segments involved. These changes were reversible and related neither to the mode of delivery, nor to the trauma of epidural cannulation.

Journal Article↗
PubMed1995

Distribution of salicylate in pigmented rabbit ocular tissues after application of a prodrug, sodium monomethyl trisilanol orthohydroxybenzoate: in vivo and ex vivo studies.

SMB (sodium monomethyl trisilanol orthohydroxybenzoate) is an organic complex of silicium and salicylate and the main component of a collyrium used in lens transparency abnormalities. Biotransformation and penetration of salicylate in the whole eyeball have been investigated in vivo after repeated instillations of those 14C-radiolabeled eyedrops. We also studied more accurately the salicylate diffusion within the lens under ex vivo conditions. In vivo experiments demonstrated that 8 to 48 hours after the last instillation, radioactivity was detectable in most tissues and remained stable except in the chorioretina. The following gradient of distribution was observed: conjunctiva > cornea > iris-ciliary body > chorioretina > lens > vitreous body > aqueous humor >> plasma and blood. The diffusion of the radiolabeled compound in lens fibres was low, but a more important retention was observed in lens capsule. Though salicylate-metabolizing activities have been demonstrated in ocular tissues, no biotransformation could be detected under our experimental conditions. The lens SA-biotransformation activity was reported to be low and we can most probably consider that, in our ex vivo pharmacokinetic study, the lens metabolite amounts were negligible compared with the salicylate levels. Under such conditions, results showed that the salicylate reached a steady-state between 6 and 12 hours of incubation, characteristic of a passive diffusion mechanism. Quantitative image analysis of lens section autoradiograms revealed a more intense labeling of the anterior part of the lens and suggests that the lens epithelium may facilitate the salicylate diffusion. Furthermore, renal excretion is important since 40% of the administered eyedrops were eliminated during the study period.

Animals↗
PubMed1995

Evaluation of antiproliferative effects of the somatostatin analogue somatuline in a rabbit model of traction retinal detachment.

As growth hormone (GH) and insulin-like growth factor type I (IGF-I) have been suggested to be involved in the development of some proliferative ocular disorders, we investigated the eventual antiproliferative properties of a long acting somatostatin analogue, somatuline or BIM23014 (IPSEN Biotech, France), in an original model of experimental proliferative vitreoretinopathy. Two studies were separately done to investigate respective effects of subcutaneously- and intravitreally administered somatuline. Injections of 10(7) human platelets freshly prepared from a unique normal donor were injected into the vitreous, cavity of pigmented rabbits. The first experiment consisted of evaluating vitreoretinal proliferation in 17 eyes from rabbits receiving subcutaneous injections of 25 micrograms/kg of BIM23014, given twice a day, from the day after injection for one month. A group of 14 eyes served as non treated controls. The second experiment was conducted in 33 eyes: 10 received intravitreally 1 microgram of somatuline given once a week for one month, 10 eyes similarly received 5 micrograms/week of somatuline, the remaining 13 eyes serving as controls with intravitreal injections of sterile saline. All animals were examined ophthalmoscopically twice a week for one month in a masked manner, and sacrificed at the end of the experiment for histological and immunohistological analyses. In all but two eyes from the subcutaneously treated group, intravitreal and preretinal membranes formed, five to eight days after platelet injection. Intravitreal proliferation progressively increased, resulting in various degrees of vitreoretinal retraction and retinal detachment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Inhibition of preretinal proliferation by free radical scavengers in an experimental model of tractional retinal detachment.

An original model of experimental proliferative vitreoretinopathy consisting of an intravitreal injection of 10(7) human platelets and 1 IU of hyaluronidase was developed in pigmented rabbits. One group of 11 eyes served as non-treated controls. Two other groups of 11 eyes each received Ginkgo Biloba extracts which are known free radical scavengers (EGb761, Ipsen, France), given orally in two doses, 50 mg kg-1 day-1 and 100 mg kg-1 day-1 respectively, from the day after the platelet injection to the end of the first month. The fourth group (11 eyes) was intravenously injected with a unique dose of 15000 U kg-1 of superoxide dismutase the day after platelet injection. All animals were ophthalmoscopically examined in a masked fashion twice a week for 1 month and killed at the end of the experiment for histological analysis. Vitreoretinal proliferation was graded according to a six-stage classification. The non-treated eyes showed a high rate of retinal detachment (11/11 eyes), with a mean final score of 3.91 +/- 0.94. Histologic examinations consistently showed retinal retraction by fibrocellular preretinal membranes spreading to both surfaces of the retina as well as preretinal neovascularization. Many cells positively reacted with anti-cytokeratin or anti-vimentin monoclonal antibodies. All three groups of treated eyes showed significantly lower scores of vitreoretinal proliferation at almost each time point of examination. At the end of the study, five retinal detachments were found in the EGb761 group at 50 mg kg-1 day-1 (mean final score 2.45 +/- 1.37), only one in the group receiving 100 mg kg-1 day-1 (mean score 1.64 +/- 1.03), and one in the SOD treated eyes. The lowest mean score found at day 28 was observed in the group receiving SOD (1.36 +/- 1.43), although this group presented during the first 3 weeks with an intense vitreous and sometimes anterior chamber inflammation. Statistical comparison between treatments did not show significant differences at most time points of the study. These results demonstrate that antioxidants may efficiently prevent preretinal proliferation, in clinicopathological entities where free radicals had not yet been shown to play a direct pathogenetic role. They are also among the first attempts for inhibiting preretinal proliferations with non-cytotoxic agents and using a non-ocular route.

Animals↗
PubMed1994

Acute tissue damage following epidural cannulation: a comparison between the midline and paramedian approach in obstetric patients.

Forty obstetric patients were randomly allocated to receive either a midline or paramedian approach to the epidural space using loss of resistance to air. Tissue trauma was assessed by blinded observers, clinically by the presence of pain and radiologically using magnetic resonance imaging (MRI). Technical difficulties with imaging reduced those who were scanned to 10 in the paramedian group and 8 in the midline group. Lateralizing signs of tissue oedema were not related to the method of epidural cannulation. There was no significant difference in localized back pain between the two groups, and this was not related to MRI findings. Pain did not persist for more than 4 days.

Journal Article↗
PubMed1994

Expression of inflammatory membrane markers by conjunctival cells in chronically treated patients with glaucoma.

PURPOSE: Recent histologic studies of conjunctival tissues in patients who have had long-term treatment for glaucoma have shown in situ an abnormal infiltration by inflammatory cells. In this study, conjunctival inflammatory antigens were investigated in impression cytology specimens from patients who have been and those who have not been treated for glaucoma. METHODS: This study included 107 eyes from 55 patients with primary open-angle glaucoma. Of these, 48 had received prolonged topical treatments, all containing benzalkonium chloride as a preservative. Seven glaucomatous eyes could be examined before any treatment. In addition, the authors examined 11 patients (21 eyes) receiving anticataract eye drops preserved with chlorhexidine and 15 normal untreated subjects (30 eyes). In all patients, immunocytochemistry was performed in impression cytology specimens, using two monoclonal antibodies against HLA-DR antigens and receptor to IgE CD23. RESULTS: None of the untreated eyes showed reactivity for either monoclonal antibody. In contrast, HLA-DR expression by conjunctival cells was found in 43 of 88 treated eyes (mean percentage of reactive cells, 70% +/- 28%) and positive staining for receptor to IgE in 26 of 68 eyes (52% +/- 28% of conjunctival cells). Results were not related to a specific treatment or combination of anti-glaucoma drugs. However, the proportion of positive specimens (3/14 for both antigens) in the group receiving chlorhexidine-containing eye drops was significantly lower than that found in the patients with glaucoma. CONCLUSION: This study showed abnormal expression of inflammatory markers without clinical inflammation at the level of conjunctival cells in repetitive contact with various anti-glaucomatous treatments and their common preservative, benzalkonium chloride. Failure in filtering glaucoma surgery was found to be related to prolonged medical treatment; therefore, a topical sensitization to preservatives and/or anti-glaucoma drugs has been hypothesized. An immunocytologic test thus could be useful for qualitative and quantitative investigation of drug-induced conjunctival inflammation and predict high-risk patients.

Adrenergic beta-Antagonists↗
PubMed1994

Influence of topical anesthesia on tonometric values of intraocular pressure.

The air pulse noncontact tonometer provides a safe and reliable method for measuring intraocular pressure (IOP), and makes it possible to avoid topical anesthesia. Based on previous reports that suggested possible anesthetic-induced IOP variations, this study was undertaken to investigate with this procedure the influence of local anesthetics on IOP and of some topically used drugs that could modify IOP values. In 212 normal or glaucomatous patients who underwent IOP measurement with a noncontact tonometer, IOP was determined before and in the first minutes following instillation of one of four tested drugs, oxybuprocaine and betoxycaine, two topical anesthetics currently used in applanation tonometry, and indomethacin suspension and metipranolol as controls. No significant effect was observed when comparing IOP values successively measured with the air pulse tonometer or 1 min after instillation of indomethacin suspension and metipranolol. In contrast a significant decrease in IOP was observed 1 and 5 min after instillation of one drop of the local anesthetics oxybuprocaine (mean IOP: 15.53 mm Hg before, 14.77 mm Hg at the 1st minute; p < 0.001) and betoxycaine (16.06 mm Hg before, 15.70 mm Hg at the 1st minute; p = 0.023). This effect was observed at least to the 15th minute, and in some patients, the decrease in IOP reached 8 mm Hg. Metipranolol only decreased IOP significantly at the 15th minute as compared to initial values, which differed from IOP variations following topical anesthesia. This phenomenon could not be related to mechanical effects of repetitive IOP measurements or massage by eyelids secondary to corneal irritation by anesthetic eye drops.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1994

[Vitreoretinal proliferation. I. Clinicopathological aspects].

Proliferative vitreoretinopathy (PVR) remains the major complication occurring after a rhegmatogenous retinal detachment, and often results in massive periretinal retraction which makes impossible any attempt in reattaching neuroepithelial layers. The most recently proposed classifications of PVR as well as clinical observations improved the understanding of PVR and suggested that some events could be of striking importance in its development, such as the size of retinal breaks, eventual haemorrhages or overdosed cryoapplications. Most interesting findings, however, resulted from the more and more powerful analysis of vitreoretinal membranes. Electron microscopy, immunohistochemistry and molecular biology techniques permitted identification of a wide variety of cellular and biological components. The majority of cells involved in PVR are from retinal or ciliary pigment epithelial, glial or inflammatory origins. Extracellular matrix are constituted with collagen, fibronectin, heparan sulfates or laminin, but they also contain growth factors, immunoglobulins and activated complement. Moreover, proliferating cells express membrane receptors to growth factors and to immunocompetent cells, which makes PVR an extraordinarily complicated biological syndrome, involving a wide range of mediators and cellular systems.

Humans↗
PubMed1994

[Vitreoretinal proliferation. II. Pathogenic hypotheses].

The pathogenesis of proliferative vitreoretinopathy remains poorly understood and a large variety of hypotheses have been developed in an attempt to investigate cellular proliferations that follow rhegmatogenous retinal detachment. Several growth promoting factors have been identified within the vitreous body and proliferative membranes from patients with PVR. Their enzymatic, chemotactic, mitogenic or proinflammatory properties make them good candidates, either alone or more probably in a synergistic manner. They may be involved at different levels in the successive stages of PVR, cell migration, proliferation or vitreoretinal contraction. Numerous ocular and even extra-ocular structures may be involved as retina, pigment epithelium, ciliary body and serum, contain large amounts of these growth factors. Immune mediated inflammatory reactions have also been described and vitreoretinal strands exert additional mechanical effects. Current pathogenetic hypotheses suggest that PVR results from a wound healing process induced by retinal breaks and detachment of the neuroepithelium, when is reached a threshold of biological stimulation. Cell proliferation is unfortunately often overstimulated and the proliferating cells invade the vitreous cavity. If surgery is not capable of efficiently blocking the proliferation, it will be autostimulated and lead to a complete vitreoretinal retraction.

Animals↗
PubMed1994

Toxicologic and pharmacokinetic analysis of intravitreal injections of foscarnet, either alone or in combination with ganciclovir.

PURPOSE: The retinal toxicity of single and repeated intravitreal injections of foscarnet was investigated. In addition, the effects of a combination of foscarnet and ganciclovir were studied, and a pharmacokinetic study to determine the ocular pharmacokinetics of foscarnet after intravitreal injection was carried out. METHODS: Forty rabbits (both albino and pigmented) were used in this study. The electroretinographic (ERG) a-waves and b-waves and oscillatory potentials (OP) were used as as indicators of retinal toxicity. Potential toxicity was also assessed by ophthalmoscopy and histologic studies (light and electron microscopy). RESULTS: The a-wave and b-wave were not deteriorated with 2.4 mg foscarnet after single or repeated injections. The OP remained unchanged. There was no ERG change after intravitreal injection of a combination of both drugs. No evidence of retinal toxicity was observed by indirect ophthalmoscopy in any case. Light and electron microscopy on semithin sections of retina failed to demonstrate any adverse effects, and showed normal organization and cytoarchitecture of all the layers of the retina without evidence of cytopathology. The ocular pharmacokinetics of foscarnet determined by noncompartmental analysis showed a 34-hour terminal elimination half-life and an apparent volume of distribution of 1.9 ml. CONCLUSIONS: Based on these results, high doses of foscarnet were not judged toxic to the rabbit retina, with single or repeated injections. Moreover, concomitant injection of the two drugs did not induce any retinal toxicity. These findings suggest that when systemic treatment is to be stopped in patients with AIDS for toxic side effects, either ganciclovir or foscarnet may be used intravitreally as an alternative. Because a combination of the two drugs has been shown to be synergistic, both ganciclovir and foscarnet might be simultaneously injected into the vitreous cavity to block progression of cytomegalovirus retinitis.

Animals↗
PubMed1993

MHC class II antigen expression by ocular cells in proliferative diabetic retinopathy.

An immunohistological study was performed on ciliary biopsies of the pars plana obtained surgically in 10 patients suffering from diabetic retinopathy and on 15 surgical specimens of pre-retinal neovascularized membranes. Using immunofluorescence and immunoperoxidase procedures, linear deposits of IgG, IgA and complement components were found in the 8 pars plana from patients with proliferative diabetic retinopathy, at the basal pole of the pigment epithelial cells and within the stroma. In contrast, these deposits were absent from normal pars plana and from the cases of background retinopathy. Moreover, pigment and non-pigment epithelial cells were found to express HLA DR and DQ determinants, in six of the eight patients with proliferative retinopathy. Immunohistological examination of pre-retinal membranes showed deposition of immunoglobulins and complement components within the connective stroma and along the new blood vessels. Endothelial cells of the newly formed vascular walls strongly expressed class II antigens on their membrane, as well as scattered stromal cells. As neither pigment epithelial cells nor retinal vascular endothelial cells normally express class II determinants, our results suggest the involvement of immunological phenomena in intraocular proliferative diseases and eventual interactions between the immune system and peptide growth factors. However, whether or not this immune reaction plays a role in the initiation or extension of intra-ocular proliferation remains to be determined.

Adult↗
PubMed1993

Growth factors in vitreous and subretinal fluid cells from patients with proliferative vitreoretinopathy.

Mechanisms accounting for the development of proliferative vitreoretinopathy (PVR) in patients with rhegmatogenous retinal detachment remain poorly understood. In a previous study, we found the presence of various growth factors in preretinal membranes that were surgically removed from patients with PVR. The present immunohistological study was undertaken in intravitreal and subretinal fluid cells from patients suffering from PVR in various stages of development, in order to seek the presence of 4 growth-promoting factors for retinal pigment epithelial cells: acidic fibroblast growth factor (FGF), epidermal growth factor (EGF), insulin-like growth factor type I (IGF-I) and transforming growth factor-beta (TGF-beta). Results were quite similar in vitreous and subretinal fluid. Acidic FGF was found in all vitreous and subretinal specimens, in 30-100% of the examined cells. Immunoreactivity for EGF could be found in 53% of intravitreal cells and 69% of subretinal fluid cells. Positive cells were seen in all vitreous specimens and in all but 1 of the subretinal fluid specimens. IGF-I-containing cells were present in 13 of 15 vitreous specimens and in 18 of 20 subretinal fluid samples (mean percentages of reactivity in positive specimens 70% and 78%, respectively). In contrast, TGF-beta 1 reactivity was found in only 8 of 15 vitreous specimens and in 11 of 20 subretinal samples. Mean percentages of reactive cells were 30% and 50%, respectively. These results suggest that several growth factors could be involved in the proliferation and migration of retinal pigment epithelial cells during the course of PVR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗