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Biomedical subjects

P Gastaud

Publications and source records attributed to P Gastaud.

At least 55 records · Page 3Linked to original sources
PubMed1995

Effect of severity of surgery on metabolic control and insulin requirements in insulin-dependent diabetic patients.

We have evaluated insulin requirements and the relationship between hormonal variables, changes in blood glucose and insulin requirements in insulin-dependent diabetic patients undergoing two degrees of severity of surgery: minor (vitrectomy) and major (gastrectomy, bowel resection, hip replacement). The study began just before induction and ended 2 h after surgery. Blood glucose concentrations were comparable in both groups but the total amount of insulin given was significantly greater in the major surgery group. Plasma noradrenaline and cortisol concentrations increased significantly during major surgery and there were significant correlations between the increase in these counter-regulatory hormones and the amount of insulin administered. We conclude that the metabolic changes occurring during surgery were small, but at the cost of a marked increase in insulin requirements during major surgery. Increased sympathetic nervous system activity seems to have been implicated in the increase in insulin requirements.

Adult↗
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

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

Comparison of two methods of i.v. insulin administration in the diabetic patient during the perioperative period.

We have examined the effects of two types of insulin therapy (continuous i.v. infusion (group A: 1.25 u. h-1) and direct i.v. bolus administration of 10 u. every 2 h (group B: 10 u./2 h)) on the metabolic and endocrine responses to surgery in 60 adult diabetic patients undergoing general anaesthesia for elective procedures. Blood glucose concentrations were measured every 15 min from just before induction of anaesthesia until 2 h after surgery. Plasma ketone bodies, lactate, pyruvate, insulin, C-peptide and counter-regulatory hormone concentrations were measured also. Blood glucose concentrations were comparable in both groups, except at 60 min, because of fluctuating blood glucose concentrations in group B. In each group, one patient became hyperglycaemic. One case of hypoglycaemia occurred in group B. There were no statistically significant differences for the other data except for C-peptide. We conclude that, during the operative period, the administration of a direct i.v. bolus of insulin 10 u. every 2 h is a simple and effective method to control blood glucose concentrations; the method can be used when an insulin infusion pump is not available.

Adult↗
PubMed1994

Intraoperative glycaemic control in non-insulin-dependent and insulin-dependent diabetes.

We have compared intraoperative glycaemic control, insulin requirements and metabolic and endocrine variables in 40 non-insulin-dependent diabetic patients (NIDDM) and 40 insulin-dependent diabetic patients (IDDM) undergoing general anaesthesia for elective procedures. Two i.v. insulin regimens were used: continuous i.v. infusion (group A: 1.25 u.h-1) and repeated i.v. boluses (10 u./2 h). Blood concentrations of glucose were measured every 15 min from just before induction of anaesthesia until 2 h after surgery. Plasma lactate and pyruvate concentrations, ketone bodies, C-peptide and counter-regulatory hormones were also measured. Glycaemia did not differ significantly in the two types of diabetes, regardless of the insulin therapy used. The amounts of insulin administered were similar in NIDDM and IDDM. There was no significant difference for other metabolic variables. Plasma concentrations of growth hormone (GH) increased significantly during surgery, especially in IDDM patients, but this change did not alter intraoperative glycaemic control. We conclude that mean glycaemic control, insulin requirements and development of ketone bodies in NIDDM and IDDM patients did not differ during the operative period, regardless of the insulin regimen used. Therefore, during the operative period, it is not necessary to modify the insulin regimen according to the type of diabetes. The consequences of increased plasma GH concentrations on glycaemic control in IDDM patients after operation are unknown.

Adult↗
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↗
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↗
PubMed1992

Immunopathological findings in conjunctival cells using immunofluorescence staining of impression cytology specimens.

The conventional technique of impression cytology provides a non-invasive method for the evaluation of conjunctival epithelium alterations. Using indirect immunofluorescence procedures two inflammatory markers, class II MHC antigens HLA DR and the receptor to IgE (CD23), were sought in impression cytology specimens obtained from 80 patients. In normal subjects conjunctival epithelial cells did not show any reactivity. Only scattered dendritic cells were found to express class II antigens but not the receptor to IgE. In contrast patients with chronic conjunctivitis of various aetiologies, mainly infectious or allergic, had 40-100% of brightly positive conjunctival cells for one or both antigens. In these cases epithelial cells and goblet cells reacted similarly. Twenty four eyes in 12 patients with idiopathic dry eye syndrome disclosed results similar to those from normal conjunctival specimens. However 18 other specimens from patients suffering from idiopathic tear deficiency but undergoing multiple substitutive treatments for dry eye had moderate to strong positivity for HLA DR and/or the receptor to IgE (20-100% of cells). As these results were independent of the degree of squamous metaplasia the expression of these membrane markers may reflect local inflammation in addition to tear deficiency, possibly due to sensitisation to the eye drops used. These immunocytological techniques thus provide useful methods of investigating conjunctival inflammation and allergy. They may constitute valuable aid in the diagnosis and appropriate treatment of ocular surface disorders.

Adult↗
PubMed1992

Immunohistological study of subretinal membranes in age-related macular degeneration.

An immunohistological study was performed on 6 specimens of subretinal membranes obtained surgically from patients suffering from age-related disciform macular degeneration. using immunoperoxidase procedures, we found in those membranes large amounts of IgG, IgA and IgE as well as C1q, C3c and C3d complement components diffusely distributed in the connective stroma and within the new blood vessel walls. Moreover, subretinal membranes contained numerous isolated HLA-DR- and -DQ-expressing cells, including glial, pigment epithelial and vascular endothelial cells. Monoclonal antibodies to immunocompetent cells disclosed only rare B and natural killer lymphocytes or suppressor-cytotoxic T cells, as well as some monocytes. These results show that immune phenomena are involved in proliferative changes associated with subretinal neovascularization. In addition, they suggest there are interactions between the immune system and peptide growth factors.

Antibodies, Monoclonal↗
PubMed1992

Transferrin receptor expression by retinal pigment epithelial cells in proliferative vitreoretinopathy.

Immunotoxins directed against a membrane marker of cell proliferation, transferrin receptor, were investigated to inhibit the growth of retinal pigment epithelial (RPE) cells in proliferative vitreoretinopathy (PVR). We undertook an immunocytological study in specimens of vitreous, subretinal fluid, and epiretinal membranes from patients with PVR to address the expression of transferrin receptor by proliferating pigment epithelial cells during the course of PVR and in normal human ocular structures. Thirty four specimens of vitreous and subretinal fluid, as well as seven epiretinal membranes, were immunocytologically examined using monoclonal antibodies to transferrin receptor. They showed a strong expression of this marker by a large majority of the cells in these two periretinal fluids (mean percentages 80 and 91% in vitreous and subretinal fluid, respectively). In contrast, only a few cells within epiretinal membranes were found to express transferrin receptor. In normal human eye sections conjunctival and corneal epithelial cells, subcapsular epithelium of the lens strongly expressed transferrin receptor, whereas RPE cells remained negative to antitransferrin receptor antibodies. A few iris or ciliary pigment epithelial cells reacted weakly. Thus, this study shows that most intravitreal and subretinal fluid proliferating cells strongly express transferrin receptor on their surface. Also confirmed is that immunotoxins to this membrane antigen could constitute potentially useful therapeutic agents in PVR.

Adult↗