PubMed Health⌕ Search

Biomedical subjects

M D Becker

Publications and source records attributed to M D Becker.

At least 19 recordsLinked to original sources
PubMed2006

[Diagnostic procedure for uveitis patients: reduction of costs by a targeted assessment of laboratory tests based on clinical findings].

BACKGROUND: Interdisciplinarity is an essential prerequisite for extensive and high-quality diagnostic work-up, therapy, and care of patients with inflammatory rheumatic disease. The ophthalmological status significantly narrows down the possible causes for the primary disease and facilitates an effective diagnostic approach. METHODS: We developed an assessment procedure according to the individual clinical findings to use as an ideal diagnostic strategy for an interdisciplinary center. To permit comparability we first introduced this new diagnostic tool in November 2002 (intervention), replacing the existing cost-intensive standard diagnostic procedure for uveitis patients. RESULTS: The average costs for laboratory tests (calculated according to GOA numbers, scale of fees for physicians) were reduced from 670+/-11 euros per patient before the intervention to 238+/-18 euros per patient after the intervention. Before intervention 16 of 31 (52%) could be assigned to a specified disease compared to 27 of 53 (51%) after the intervention. With our strategy we were able to obtain a 64% reduction of costs in the diagnostics of uveitis patients without a deterioration of our diagnostic quality. CONCLUSION: It is possible to reduce costs and still improve the care of uveitis patients by using a targeted assessment according to the individual clinical findings.

Clinical Laboratory Techniques↗
PubMed2005

[Strategies for the immunosuppressive therapy of intraocular inflammation].

Over the past two decades, therapeutic options for the treatment of intraocular inflammation (uveitis) have developed into a highly differentiated approach with an increasing number of drug options. In contrast to some other common sight-threatening ocular diseases, the majority of patients with uveitis can expect to receive treatment which will positively alter the course of their eye disease. Besides corticosteroids (CS) as primary systemic treatment, the most popular CS-sparing drug appears to be MTX in the treatment of uveitis. This paper suggests a strategy for the therapeutic approach to treating patients with intraocular inflammation. A table summarizes detailed information about mechanisms of action, dosage, and side effects, etc.

Adrenal Cortex Hormones↗
PubMed2005

[Computer-based system for monitoring the course of intraocular inflammation].

BACKGROUND: Until now, there has been no consistent rating system for changes of intraocular inflammation. We present such a computer-based system. METHODS: This program is based on a FileMaker database. It is made of anterior and posterior uveitis scores on the basis of published evaluation guidelines of the International Ocular Inflammation Society (IOIS). An anterior uveitis score consisting of anterior chamber cells, flare, and perilimbal injection on the one hand and a posterior uveitis score consisting of vitreous haze, macula, and optic nerve head edema on the other hand are calculated. After adding visual acuity, intraocular pressure, and systemic dose of corticosteroids, all parameters can be visualized by a radar graph. RESULTS: This system of documentation is easy to handle and presents a simplified version of the disease course. The abstract visualization enables the patient to better understand the therapeutic management. CONCLUSIONS: The program presented here offers good opportunities for standardized monitoring of the disease course.

Computer Graphics↗
PubMed2005

[Fuchs uveitis syndrome--heterochromia is no "conditio sine qua non"].

Fuchs uveitis syndrome (FUS) is typically a unilateral, chronic, low-grade inflammation of the anterior segment which manifests in young adulthood. It is underdiagnosed because of its variable clinical spectrum. Although it can mimic various forms of anterior uveitis, it is important to make the correct diagnosis, based on clinical grounds, because both the management and prognosis differ from those of other uveitides. While its etiology remains unknown, it is possible that the disease has multiple causes that lead through different pathogenic mechanisms to the same clinical entity. Although many patients do not require treatment, it is not a benign condition, as often perceived. The high incidence of glaucoma makes it mandatory that all patients with FUS should be screened at regular intervals, even if they are not being actively treated and are relatively asymptomatic.

Diagnosis, Differential↗
PubMed2005

Interferon as a treatment for uveitis associated with multiple sclerosis.

AIM: In addition to optic neuritis (ON), multiple sclerosis (MS) may also involve the eye with a typically bilateral intermediate uveitis. The aim of this pilot study was to evaluate the efficacy of type I interferons (IFN) for the treatment of MS associated uveitis. METHODS: In this non-randomised, retrospective observational case series 13 patients (eight female, five male) with proved MS and associated uveitis from five uveitis centres who were treated with interferon beta1a were included. Visual acuity (VA), cell count in the aqueous humour and vitreous, as well as the presence of cystoid macula oedema (CMO) were observed. RESULTS: All except one patient had a bilateral form of intermediate uveitis (total of 24 eyes). Seven patients had documented CMO before IFN treatment (n = 13 eyes). Median duration of treatment was 24.6 months (range 7.9-78.7). VA improved in 17 eyes (comparing VA before therapy and at last follow up); while 10 eyes (36%) improved >or=3 Snellen lines. Aqueous cell count improved by 1.2 (SD 1.1) grades in all eyes. Vitreous cell count improved by 1.7 (1.4) in all eyes. Only two patients still had minimal CMO on last follow up angiographically. CMO resolved after or during IFN treatment in nine eyes. CONCLUSIONS: IFN has been shown to have beneficial effects in patients with MS and/or ON. As shown in the models of experimental allergic encephalomyelitis (EAE) and uveitis, the neurological and ophthalmological manifestations seem to share similar pathogenic mechanisms. Treatment of MS associated uveitis with IFN appears to have beneficial effects on VA, intraocular inflammation activity, and the presence of CMO.

Adult↗
PubMed2003

[Diagnostic vitrectomy in uveitis: possibilities of molecular biology].

Recent developments in molecular biology allow novel diagnostic approaches in intraocular inflammation. Genetic markers as well as species-specific sequences are used for the diagnostics of infection or masquerade syndromes. This article provides state-of-the art information about diagnostic vitrectomy.

Biopsy↗
PubMed2003

[Therapeutic vitrectomy in uveitis: current status and recommendations].

With the advent of modern vitreoretinal surgical techniques, the spectrum for surgical intervention in various forms of uveitis has been notably expanded. Removal of optically relevant vitreous opacities, improvement of secondary macular edema, delamination of epiretinal membranes, and release of traction in the presence of abnormal vitreoretinal adhesions represent indications for vitreoretinal procedures in uveitis patients. Furthermore, retinal and choroidal biopsies may be obtained if the precise etiology is unknown. This in turn offers the opportunity to better target pharmacological interventions. Combined cataract surgery or intravitreal implantation of drug devices may also be of therapeutic benefit. So far no prospective, controlled clinical trials have been performed to precisely evaluate the role of pars plana vitrectomy (ppV) as a single or combined surgical procedure in patients with intraocular inflammation. Inconsistent data exist regarding prognostic determinants and the role of perioperative immunosuppression. Here, the current knowledge on the subject is reviewed and critically discussed, and recommendations for patient management are given. Further studies are needed.

Combined Modality Therapy↗
PubMed2002

Simultaneous in vivo imaging of leukocyte migration: heterogeneity among iris, limbus, and choroid vessels.

PURPOSE: Endothelial cells of different vascular systems may express site-specific adhesion molecules to attract leukocyte subsets. This study describes a method to visualize and compare leukocyte-endothelial interactions in three vascular beds within the same eye in mice. METHODS: Digital in vivo fluorescence microscopy was used to record a trans-corneal iris view, a superficial limbus view, and a trans-scleral anterior choroid view of mouse tissue. Uveitis was induced by intravitreal injection of E. coli endotoxin into BALB/c mice. Leukocytes were labeled systemically with SYTO-16 or rhodamine 6G. Leukocyte rolling and sticking were quantified at baseline and 4, 6, and 24 hours after endotoxin injection. RESULTS: In a normal animal, the limbus had 18 times the number of rolling leukocytes and 6 times the number of sticking leukocytes relative to the iris. All three vascular beds were affected by intravitreal injection of endotoxin. Although they each showed increased numbers of rolling and sticking cells, the levels and kinetics of these increases differed. Rolling peaked at 6 hours in the iris (34-fold increase from baseline) and limbus (7-fold increase) but was maximal in the choroid earlier with a 16-fold increase. Sticking was maximal at 4 hours for iris (96-fold increase) and choroid (19-fold increase) but peaked in the limbus at 6 hours (47-fold increase from baseline). CONCLUSIONS: This study demonstrates that leukocyte-endothelial dynamics are not the same in different vascular beds in the normal mouse eye. Furthermore, site-specific differences in responses to intravitreally injected endotoxin, beyond what can be readily explained by differential distribution of endotoxin, were observed. The methodology can be used to test the hypothesis that endothelial cells within the eye have site-specific patterns of adhesion molecule expression.

Animals↗
PubMed2001

Intraocular in vivo imaging of activated T-lymphocytes expressing green-fluorescent protein after stimulation with endotoxin.

BACKGROUND: Intravital microscopy allows imaging of specific cell populations in vivo. The value of this technique is well established, but would be enhanced if one could distinguish functional states of cells in vivo. Interleukin-2 (IL-2) is expressed upon stimulation of T-cells and is a commonly used marker for T-cell activation. This study tests the use of enhanced green fluorescent protein (GFP) as a reporter gene for interleukin-2 (IL-2) expression in vivo. METHODS: Characterization of mice that have the GFP gene under the control of IL-2 regulatory sequences has previously been published. Uveitis was induced by injection of E. coli endotoxin into the vitreous of these IL-2/GFPki transgenic mice. Four hours later, 3 microg of recombinant mouse IL-2 was injected into the anterior chambers of one group of mice. In vivo imaging of infiltrating cells in the iris stroma was performed with fluorescence microscopy at 6, 24, 48, and 72 h after endotoxin injection. The absolute number of fluorescent cells per mm2 was evaluated. RESULTS: Eyes with endotoxin-induced uveitis had cells that expressed GFP and were identifiable by intravital microscopy. The fluorescent cells were exclusively seen in the subset of cells that had infiltrated the iris stroma or arrested along the vascular endothelium. The number of GFP-positive infiltrating cells in the iris increased from undetectable at baseline to 0.5 cells/mm2 at 6 h and 1.3 cells/mm2 at 72 h. The animals that received endotoxin as well as IL-2 tended to have more GFP-positive cells at the 48-h and 72-h time points, but these differences were not statistically significant CONCLUSIONS: GFP is commonly used as a reporter gene for in vitro expression assays. The results presented here document that transgenic mice with GFP under the control of IL-2 regulatory elements can be used with intravital microscopy for in vivo expression assays that allow detection of activated T-cells at multiple time points within the same animal. This provides a novel method for temporal and spatial studies on the state of cell activation in inflammatory responses.

Animals↗
PubMed2001

Inhibition of leukocyte sticking and infiltration, but not rolling, by antibodies to ICAM-1 and LFA-1 in murine endotoxin-induced uveitis.

PURPOSE: Cell-adhesion molecules are critical elements in intravascular rolling and sticking of leukocytes during acute inflammation. In this process, selectins are thought to be involved in initial adhesion and rolling, and integrin-Ig superfamily interactions are believed primarily to mediate stronger adhesion and transendothelial migration. This study clarifies the role of two adhesion molecules, intercellular adhesion molecule (ICAM)-1 and leukocyte functional antigen (LFA)-1, in endotoxin-induced uveitis (EIU). METHODS: Intravital microscopy was used to record the movement and location of leukocytes in the irises of mice with uveitis induced by intravitreal injection of 250 ng Escherichia coli endotoxin. Each mouse concurrently received an intraperitoneal injection of monoclonal neutralizing antibodies for ICAM-1, LFA-1, or both or control irrelevant antibodies. RESULTS: Mice treated with endotoxin and control antibodies had an inflammatory response that was clearly present at the 6- and 24-hour time points and was mostly resolved by 48 hours. Mice that received anti-ICAM-1 or anti-LFA-1 had significantly fewer cells infiltrating their irises at 6 and 24 hours. Detailed analysis of the 6-hour time point recordings revealed that neither anti-ICAM-1 nor anti-LFA-1 significantly reduced the number of leukocytes rolling on venule endothelial surfaces, but the treatments reduced the number of firmly adherent cells. CONCLUSIONS: These data confirm previous reports that ICAM-1 and LFA-1 are important mediators of EIU. The dynamic in vivo images clearly support the hypothesis that integrin-mediated cell adhesion is more critical for the firm adhesion of sticking cells than for leukocyte rolling.

Acute Disease↗
PubMed2000

Digital video-imaging of leukocyte migration in the iris: intravital microscopy in a physiological model during the onset of endotoxin-induced uveitis.

The process of inflammation is accompanied by an alteration of leukocyte-endothelial dynamics. Reciprocal changes in the endothelium and the white cell permit the leukocyte to relinquish its normal free-flowing state in order to roll, arrest, and emigrate through the endothelium. Although intravital microscopy is an established method to observe this process, the eye has been under-utilized for this purpose. Iris vasculature can be videophotographed without the artifact of trauma. We used rhodamine 6G in vivo staining of leukocytes from BALB/c mice in a model of inflammation induced by intravitreally injected endotoxin. Digital video technology was used to record observations at baseline, 2 h, and 4 h after the endotoxin injection. Off-line analysis of microhemodynamic parameters established that the percentage of venules exhibiting rolling increased significantly from 4% at baseline to 34% at 2 h and 82% at 4 h after endotoxin injection. We found a marked increase in leukocyte arrest within 4 h (601+/-119 cells per mm(2) vs. 2+/-1 cells per mm(2) in control animals). Although shear stress differs minimally between iris arterioles and venules, both rolling and arrest occurred preferentially in venules indicating that shear stress is not the dominant factor for determining cell adhesion. Compared to previous reports on intravital microscopy, our methodology includes refinements or advantages in visualizing cells that have transmigrated as well as the avoidance of surgical trauma. The resolution and quantifiable nature of this technique are such that the methodology can be applied to repetitive observation of leukocyte-endothelial dynamics during an immune response.

Angiography↗
PubMed2000

Anti-rat ICAM-1 antibody does not influence the course of experimental melanin-induced uveitis.

PURPOSE: Experimental melanin-induced uveitis (EMIU) is a T cell-mediated rat model of acute anterior uveitis. We investigated the possibility of preventing the inflammation with monoclonal antibody directed against rat intercellular adhesion molecule 1 (ICAM-1). METHODS: To induce EMIU, Lewis rats were immunized with bovine ocular melanin extract (250-500 microg). Each day from day 6 post-immunization, rats were injected intraperitoneally with anti-ICAM-1 monoclonal antibody (IA29) or normal mouse serum, and examined with a slit-lamp biomicroscope. On the first day of clinical inflammation, intravital microscopy of iris vasculature was performed on each animal following intraperitoneal injection of rhodamine 6G. At the peak of clinical inflammation, rats were killed, and eyes were examined histologically. Binding potency of IA29 was tested by flow cytometry using concanavalin A-stimulated rat T cells. Immunohistochemical staining was used to detect IA29 on rat uveal vascular endothelium. RESULTS: The ability of IA29 to bind T cell blasts was present to a 1:2000 dilution, and IA29 was readily detectable on uveal vascular endothelium following systemic administration. However, there was no significant difference (p > 0.05) in incidence, time of onset, or severity or histological appearance of EMIU for the rats treated with IA29 when compared with the control rats. Intravital microscopy revealed sticking of leukocytes in the iris vasculature in both groups. CONCLUSIONS: We were unable to demonstrate an inhibitory effect of anti-rat ICAM-1 antibody on the outcome of EMIU. Our observations may reflect a redundancy in the adhesion molecule profile responsible for this uveitis.

Animals↗
PubMed2000

Current and future trends in the use of immunosuppressive agents in patients with uveitis.

Therapeutic trials for uveitis are seldom performed because of the relative rarity of the disease and its heterogeneity. Promising new approaches to therapy include cytokine or cytokine receptor inhibition; cytokine addition (alpha-interferon or interleukin-10); novel anti-metabolites; combination therapies; intravenous immunoglobulin; intravitreally inserted corticosteroid implants; and oral tolerance. Additional modalities or targets that deserve further testing include T-cell subsets, adhesion molecules, accessory molecules in antigen presentation, novel inflammatory mediators, inducers of apoptosis, photodynamic therapy, and neuroprotective agents.

Apoptosis↗
PubMed2000

Reduced leukocyte migration, but normal rolling and arrest, in interleukin-8 receptor homologue knockout mice.

PURPOSE: To determine the role of the murine interleukin-8 receptor homologue (mIL-8Rh, neutrophil chemokine CXC receptor 2) in leukocyte migration using intravital microscopy in a standardized model of eye inflammation, endotoxin-induced uveitis (EIU). METHODS: Two hundred fifty nanograms of E. coli endotoxin was injected into the vitreous of knockout mIL-8Rh(-/-) (n = 7) mice or heterozygous littermate mIL-8Rh(+/-) controls (n = 7). Intravital microscopic examination of iris microvasculature was performed at baseline and 6 and 24 hours after endotoxin injection. The numbers of rolling (cells/mm2 endothelial surface/min), sticking (cells/mm2 endothelial surface), and infiltrating cells (cells/mm2 iris tissue) were evaluated by digital off-line quantification. RESULTS: The number of infiltrating cells was significantly reduced in mIL-8Rh(-/-) mice: 406 +/- 77 cells/mm2 at 6 hours and 242 +/- 50 cells/mm2 at 24 hours in mIL-8Rh(+/-) mice versus 14 +/- 4 cells/mm2 at 6 hours and 38 +/- 11 cells/mm2 at 24 hours in mIL-8Rh(-/-) mice (P < 0.001). In contrast, the absence of the IL-8 receptor homologue did not reduce rolling or sticking. CONCLUSIONS: Iris rhodamine angiography allows precise quantification of leukocyte-endothelial dynamics in the absence of surgical trauma. IL-8 and its homologues are known to be potent signals for leukocyte migration. Although IL-8 has previously been implicated in cell adhesion, video imaging in vivo demonstrated that deletion of the IL-8 receptor homologue had minimal effect on rolling or arrest in this model of inflammation.

Animals↗
PubMed2000

The role of T cells in autoimmune uveitis.

Autoimmune diseases result from the activation of self-reactive T cells recognizing autoantigens or foreign antigens cross-reactive with an autoantigen. T cells are thought to play a major role in autoimmune diseases in different organs, including the eye. This review focuses on the role of T cells in autoimmune uveitis in humans and in animal models of experimental autoimmune uveitis. Since rheumatoid arthritis is an autoimmune disease that has been studied far more extensively than uveitis, we have also included a review of clinical and experimental observations relevant to that disease.

Animals↗
PubMed2000

The tyranny of the anecdote: Waldenstrom's macroglobulinemia and scleritis.

A 49-year-old male developed a bilateral scleritis that eventually involved the optic nerve and was associated with cotton wool spots. Investigation of a markedly elevated erythrocyte sedimentation rate revealed a diagnosis of Waldenstrom's macroglobulinemia. Although it was plausible to believe that the two rare diseases were causally related, the scleritis resolved while the gammopathy progressed.

Biomarkers↗