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Biomedical subjects

A Bron

Publications and source records attributed to A Bron.

At least 37 records · Page 2Linked to original sources

[The circadian effects of antiglaucomatous drugs].

PURPOSE: To collect data reflecting the current knowledge on the interactions of medical antiglaucomatous therapy and circadian variations. METHOD: Review of the available literature published on this topic in common electronic databases. RESULTS: The IOP-reducing effect of a molecule throughout the day depends on many parameters and still remains poorly investigated. It is well known that beta-blockers have a poor efficacy at night, while prostaglandins prevent nocturnal IOP variations because of their original mechanism. DISCUSSION: The lack of a 24-hour IOP recording device limits our ability to track the effect of antiglaucomatous drugs over 24 hours, an important point because these antiglaucomatous drugs vary in terms of their capacity to reduce IOP over a 24-hour period. CONCLUSION: Assessing the effect of antiglaucomatous therapy on a 24-hour basis remains very difficult. However, in the next few Years, this could become an emerging focus point in the management of glaucoma.

Adrenergic beta-Antagonists↗

[Efficacy and safety of substituting a twice-daily regimen of timolol with a single daily instillation of nonpreserved beta-blocker in patients with chronic glaucoma or ocular hypertension].

AIM: To evaluate the efficacy and safety of a single daily instillation of nonpreserved timolol in patients with chronic glaucoma or ocular hypertension previously treated with a twice-daily regimen of timolol 0.25% or 0.50%. PATIENTS AND METHODS: A prospective open clinical trial was undertaken by 220 ophthalmologists in 435 patients with chronic glaucoma or ocular hypertension controlled with twice-daily instillations of timolol 0.25% or 0.50%. In this population, the previous regimen was substituted with a single daily instillation of preservative-free timolol 0.25% or 0.50% for 3 months. The changes in intraocular pressure (IOP) were recorded as well as local and systemic tolerance and patient compliance. RESULTS: It was found that 398 patients (93.6%) maintained stable IOP: in 92%, IOP increased no more than 2 mmHg. The mean IOP was 17.0 +/- 2.2 mmHg at D0, 16.5 +/- 2.4 mmHg at D28/42 and 16.6 +/- 2.4 mmHg at D84. The proportion of patients with at least one ocular symptom upon instillation or at another time decreased (p<0.0001 and p=0.03, respectively). The proportion of conjunctival hyperemia reduced from 24.4% to 14.6% (p=0.0002). The rate of folliculopapillar reactions and superficial punctate keratitis was halved (p=0.005 and p=0.02, respectively). CONCLUSION: During this study in daily practice, the switch from a twice-daily regimen of timolol to a once-daily application maintained stable intraocular pressure with a notable improvement in tolerance.

Adrenergic beta-Antagonists↗

[Glaucoma and ocular hypertension: the importance of intraocular pressure in treatment decisions in France].

PURPOSE: Several recent clinical studies have shown the benefit of lowering intraocular pressure in both ocular hypertensive and glaucoma patients. However, in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT), there is no consensus on the value of intraocular pressure (IOP) to be reached to prevent the progression of visual field defects. This IOP value, called target IOP, is defined by the ophthalmologist according to the patient and the progression of the disease, without a clear explicit justification of this decision. In France, ophthalmologists' education is mainly based on scientific meetings and the European Guidelines. This study was conducted to investigate the position of the IOP target in the treatment strategy for patients with glaucoma or OHT. MATERIAL: and methods: A cross-sectional descriptive survey was conducted in France among ophthalmologists in private practice. Patients with simple OHT or with OAG who required an initiation or a modification of treatment were included. RESULTS: We included 1735 patients (805 males, 46.4%) in the study. An OAG was diagnosed in 1338 patients (77.1%) and a simple OHT in 397 patients (22.9%). The patients with OAG were older than the OHT patients (65 years vs 61.7 years, p<0.0001). Most patients (73.5%) were included for treatment modification (77.5% of the patients with OAG and 59.9% of the patients with simple OHT; p<0.0001). The main reason for treatment change was an unsatisfactory IOP value. The main therapeutic objective was to reach a target IOP in 46.0% of the patients. The choice of the ocular hypotensive drugs depended on the IOP value in 51.9% of the patients. When the treatment was modified, monotherapy was preferred in 60.8% of the patients. CONCLUSION: Among ophthalmologists, the main objective for the treatment of patients with simple OHT or with OAG was to reach a target IOP. About half the participants were used to set up a target pressure for their patients. This fairly good ratio shows the comprehensiveness and the adaptation of our colleagues to relatively new concepts in treating and managing patients with ocular hypertension or chronic open-angle glaucoma. If a modification in the treatment was necessary, then monotherapy was preferred. This decision was motivated by the efficacy of the treatment but also by expected better patient compliance.

Adult↗

[Glaucoma and quality of life].

Glaucoma is a serious ocular disorder potentially leading to blindness. Measuring the quality of life of patients with glaucoma is important because it makes it possible to evaluate the impact of the disease and its treatment on the patient's everyday life. Hitherto, this was done using generic scales, or those developed for other diseases; but no scale suitable for glaucoma was available. The recently developed GlauQOL scale is now available. We present the short version of this questionnaire adapted to individual use within an ophthalmology consultation setting.

Glaucoma↗

[Trefoil factor family gene and peptide expression in pterygium].

PURPOSE: Trefoil factor family (TFF) peptides (formerly P-domain peptides; trefoil factor) are small (7-12 kDa) protease-resistant secreted peptides designated pS2 (or TFF1), SP (TFF2) and ITF (TFF3). Human conjunctival goblet cells (GCs) are known to synthesize TFF, but TFF expression by these cells has not been studied in pathological conditions. We quantified trefoil factor family (TFF) gene transcripts in pterygium, and we immunolocalized TFF protein. METHODS: Eleven pterygium specimens were studied, together with 19 biopsy specimens of normal human conjunctiva as controls. TFF1 (pS2), TFF2 (spasmolytic peptide) and TFF3 (intestinal trefoil factor) mRNA expression was semiquantified by means of reverse-transcription polymerase chain reaction amplification (RT-PCR). TFF1, TFF2 and TFF3 mRNA levels were determined individually, relative to beta2 microglobulin housekeeping gene mRNA (internal standard), by coamplification of the target fragments and beta2 microglobulin in the same tube. Five pterygia and five normal human conjunctival biopsy specimens were also analyzed for TFF1 and mucin (MUC5AC) protein expression by immunostaining with monoclonal antibodies. Anti-PS2 (Zymed Laboratories, San Francisco), a mouse monoclonal antibody (MAb) against the 30 C-terminal amino acids of human TFF1, and P2802 (provided by Doctor Marie-Christine Rio, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM, Strasbourg, France), a mouse MAb directed against a synthetic peptide corresponding to the last 28 amino acids of TFF1, were used at 1/20 dilution. A mouse monoclonal antibody directed against the peptidic core of gastric M1 mucin was used as previously described. M1 immunoreactivity is encoded by the MUC5AC gene. RESULTS: TFF1 and TFF3 mRNA was expressed in all normal conjunctival and pterygium specimens. TFF2 mRNA was not expressed by either sample type, but was expressed by the positive control (human stomach cDNA). TFF1 mRNA expression was stronger in pterygium than in controls (p=0.02). TFF3 mRNA expression was similar in the two sample types (p=0.89). TFF are coexpressed and act in concert with mucins to protect mucous epithelia and trigger wound-healing responses. Inflammation and ulceration of the gastrointestinal tract are associated with increased TFF expression. Conjunctival GCs secrete TFF in both pigs and humans. We found that TFF1 mRNA was overexpressed in pterygium relative to healthy conjunctiva, whereas the TFF1 immunostaining patterns were similar. TFF1 protein expression was confined to goblet cells. However, whereas all GCs were positive for MUC5AC, not all GC were labeled by anti-TFF1 mAbs in either normal conjunctiva or pterygium. The observed TFF1 mRNA overexpression in pterygium was not associated with abnormal TFF1 peptide localization. Increased MUC5AC protein expression would be expected in pterygium, because of increased GC density. Indeed, in conjunctival diseases such as dry-eye syndrome in which GC density is decreased, mucin secretion is also decreased. This could explain the increased expression of TFF1 mRNA in pterygium, although not all GCs expressed TFF1 protein. TFF proteins are copackaged within mucous cell granules; TFF1 preferentially colocalizes with MUC5AC, and TFF3 with MUC2. However, we found some cell granules containing MUC5AC but not TFF1. The proportion of TFF1-negative GCs was similar in pterygium and normal conjunctiva. The normal TFF3 mRNA expression in pterygium was unexpected and suggests that only GCs involved in TFF1 secretion are overrepresented in this pathological tissue. TFF2 mRNA was undetectable in both normal conjunctiva and pterygium, possibly because of its copackaging in mucous cell granules and its preferential cosecretion with MUC6, which is not expressed in the conjunctiva. CONCLUSION: As in normal conjunctiva, the TFF1 and TFF3 genes are expressed by conjunctival goblet cells in pterygium, contrary to the TFF2 gene. Only TFF1 gene expression was elevated in pterygium compared to normal conjunctiva.

Adult↗

[Comparison of latanoprost monotherapy with timolol-dorzolamide combination in patients with open-angle glaucoma or ocular hypertension].

PURPOSE: To compare the efficacy and safety of latanoprost monotherapy to dorzolamide combined with timolol from pooled data of five multicenter, randomized, 3-month, observer-masked trials with identical study design. METHODS: Patients who were on a beta-blocker or dual therapy where one agent was a beta-blocker were eligible after a 2- to 4-week run-in period on timolol 0.5%, twice daily. Patients then either discontinued timolol treatment and received latanoprost monotherapy n=345) or continued on timolol and received dorzolamide add-on therapy (n=352). Data from these 697 patients were included in the meta-analysis. RESULTS: From an overall baseline of 22.8mmHg, the mean IOP reduction was 4.8mmHg (21%) in latanoprost-treated patients and 4.1mmHg (18%) in timolol + dorzolamide-treated patients p<0.001). A reduction in diurnal IOP of >=20% was achieved in 54% of the latanoprost-treated patients compared with 44% of the timolol + dorzolamide-treated patients. There was no marked difference between the two groups in the incidence of ocular and systemic events. CONCLUSION: This meta-analysis provides further support that a switch to latanoprost monotherapy can be an alternative to combined treatment with timolol + dorzolamide.

Antihypertensive Agents↗

[Ocular hypertension and glaucoma: the contribution of large studies to daily practice].

Official guidelines to manage and treat various clinical presentations of glaucoma and ocular hypertension are not currently in wide use. Several well-designed clinical trials have been published recently which can provide ophthalmologists with therapeutic recommendations. In the field of ocular hypertension, three major and historic studies are reported and discussed in this review. A more recent study undertaken in Sweden and the design of the Ocular Hypertension Treatment Study (OHTS) are reviewed as well, although the final results of this important trial have not yet been published. The conclusions of the Collaborative Normal Tension Study Group (CNTSG) have been expected for a long time since this disease is difficult to manage; a 30% reduction in baseline intraocular pressure avoids further deterioration of the visual field in most patients. Other studies have dealt with different strategies in open angle glaucoma. The Advanced Glaucoma Intervention Study (AGIS) has investigated different therapeutic sequences in advanced glaucoma while the Collaborative Initial Glaucoma Treatment Study (CIGTS) and the Early Manifest Glaucoma Trial (EMGT), still in progress, have evaluated the efficacy and safety of surgery versus medical treatment and treatment versus no treatment, respectively, in new and low-grade glaucoma. These long-term studies have led to a better approach to ocular hypertension, normal tension glaucoma, initial glaucoma, and advanced glaucoma. This review presents the characteristics of these clinical studies, points out the problems linked to giving a fair and practical interpretation, and attempts to draw useful guidelines for daily clinical practice.

Clinical Trials as Topic↗

[Creating a specific quality-of-life questionnaire in patients with glaucoma: item generation].

The methods for developing Health-Related Quality-of-Life (HRQoL) measures and their application in medical research have demonstrated their utility in various chronic, progressive, or life-threatening diseases. The efforts made to allow the patient's perspective to be included in the methodological framework of evidence-based medicine have been successful. The assumption of a strong relationship between clinical status and daily life is certainly valid in ophthalmology. However, there is a lack of specific HRQoL measures dedicated to ophthalmic diseases. Our work aimed at creating the first Glaucoma-specific Quality of Life scale - the Glau-QoL questionnaire - to provide researchers and physicians with a comprehensive, practical, and validated tool. This article describes the first stage of the process, which consisted in generating items and formatting them in order to create a questionnaire that exhaustively covers the relevant concepts. The whole process was conducted by an expert committee including clinicians and methodologists. The standard recommendations in the development of a HRQoL questionnaire were followed: we first identified existing tools and performed a preliminary collection of concepts from the published literature; we then designed an interview guide with the help of clinicians; a trained psychologist interviewed 22 patients at various disease severity stages (from isolated hypertonic to severely impaired); the interviews were tape-recorded and scripted; general domains and related detailed concepts were identified from the script; they were then analyzed and organized; the format of the questionnaire was set up; and questions were derived from the patient's verbatim to capture the identified detailed concepts. The test questionnaire was applied to seven patients for cognitive debriefing. We finally amended the test questionnaire and designed the pilot questionnaire according to the patients' tests and the clinician's review. The test questionnaire was well accepted by the patients, despite a completion duration ranging from 14 to 35 minutes. The pilot questionnaire contained 151 items, grouped into 5 sections: (1) vision problems, physicians, and daily treatment (49 items); (2) activities of daily living (37 items); (3) self-expression (37 items); (4) vision problems and mood (14 items); and (5) other questions (14 items). The next step of our work will be the item reduction process and the psychometric validation of the Glau-QoL questionnaire.

Activities of Daily Living↗

[Treatment of glaucomas].

Glaucomas have to be considered as the final common pathway of various diseases rather than a single disease. Therefore treating glaucomas remains a difficult task since the clinical presentations of the glaucomas are very different without any definite known cause; only some risk factors are believed to lead to the glaucomas. Among these risk factors intraocular pressure is really possible to treat and focuses all our therapeutic attempts. The general practitioner and the ophthalmologist have to work close together to better evaluate the systemic adverse effects of topical medications and to avoid harmful drugs for the outcome of the glaucomas.

Family Practice↗

[Cogan's syndrome. A case report].

Cogan's syndrome is an inflammatory disease that is characterized by ocular inflammation (typically interstitial keratitis) and is associated with Ménière-like vestibuloauditory dysfunction. Ocular inflammation usually resolves after several weeks or months but deafness is often irreversible. We report on a case of Cogan's syndrome in a 23-year-old woman who initially presented with bilateral anterior uveitis, an unusual clinical feature for this disease. We discuss the clinical aspects, the pathogenic mechanisms, the laboratory investigations, the differential diagnosis, and the treatment of Cogan's syndrome.

Adult↗

[How to prevent and treat glaucoma surgical failures?].

Although many improvements have been made to filtering surgery in glaucoma, some post operative complications do occur quite often. Patients need careful and frequent follow-up to assess and treat the early complications that may occur after glaucoma surgery. Over the medium and long term, insufficient verification of the intra ocular pressure signals the failure of the initial surgery. In this article, we review the diagnostic tools useful for detecting the early and late failures of glaucoma surgery and we provide recommendations for their treatment.

Glaucoma↗

[Drugs and the eye].

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Adrenal Cortex Hormones↗

Bronchial angiogenesis in severe glucocorticoid-dependent asthma.

To examine the role of the bronchial microvasculature and adhesion molecule expression in severe asthma, the authors have performed an immunohistochemical study on bronchial biopsies comparing 15 glucocorticoid-dependent asthmatics, 15 mild asthmatics and eight control subjects. Serially cut glycol methacrylate-embedded sections were stained with monoclonal antibodies identifying the vessel marker EN-4, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, E- and P-selectin. Sections were also stained for lymphocyte function associated antigen (LFA)-1 and very late antigen (VLA)-4. By comparison with mild asthma and nonasthma, severe asthma was characterized by increased numbers of submucosal vessels (p=0.009) which was associated with increased numbers of vessels expressing ICAM-1 (p=0.005). A highly significant correlation was found between the total number of EN-4+ vessels and the vessels expressing ICAM-1 (r=0.85, p=0.01). In contrast, E-selectin expression was lower in severe as compared with mild asthma (p=0.01) but not different from normal. No differences were found between the three groups in the expression of VCAM-1 and P-selectin nor in numbers of LFA-1+ and VLA-4+ cells. The results of this study support the notion that mucosal neovascularization is an important feature of airways remodelling in severe asthma. This is associated with a relatively higher density of vessels expressing intercellular adhesion molecule-1, although the expression of this adhesion molecule per vessel was not raised.

Adolescent↗

Low-dose methotrexate treatment in severe glucocorticoid-dependent asthma: effect on mucosal inflammation and in vitro sensitivity to glucocorticoids of mitogen-induced T-cell proliferation.

The authors have investigated whether the steroid-sparing effect of methotrexate (MTX) in severe orally glucocorticoid-insensitive asthmatics may be accounted for by the ability of this drug to increase the T-cell responsiveness sensitivity to dexamethasone in vitro. In addition the authors have investigated whether low-dose MTX treatment is associated with anti-inflammatory effects in peripheral blood and the bronchial mucosa. In eight patients with severe atopic asthma, using > or =15 mg x day(-1) prednisolone, the inhibitory effect of dexamethasone on mitogen stimulated peripheral blood mononuclear cells (PBMC) in vitro was tested before and after 8 weeks of uncontrolled treatment with MTX. Endobronchial biopsies were taken before and after MTX therapy in seven subsequent patients, and analysed using immunohistochemistry. In eight patients, serum was drawn for measuring levels of free interleukin (IL)-8. The in vitro sensitivity of PBMC to dexamethasone (at 1.6 x 10(-9) and 3.2 x 10(-10) mol x L(-1)) was significantly lower in the asthmatics before treatment when compared with the control subjects (p=0.03 and =0.001) but increased significantly after MTX treatment (p=0.04 and =0.02) to normal responsiveness. This was not associated with a decrease in peripheral blood T-cell numbers or activation. Except for a significant increase in the numbers of CD3+ (p=0.04), no significant numerical changes in activated T-cells, eosinophils, or mast cells were found (p>0.05). However, MTX treatment was associated with a significant fall in serum levels of free IL-8 (p=0.03). It is hypothesized that the steroid-sparing effect of methotrexate originates from increased sensitivity of lymphocytes to the inhibitory effects of glucocorticoids. The absence of an inhibitory effect on inflammatory cells in blood and mucosa suggests that this effect is achieved by modulating cell function rather than cell number.

Adolescent↗

[Accidental laser burn].

A student suffered an accidental parafoveal laser burn during a physics experiment. We discuss here the clinical features and management and follow-up. This case presents a good example of photic injuries which can occur in many different settings.

Accidents↗