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Biomedical subjects

U Pleyer

Publications and source records attributed to U Pleyer.

123 records · Page 7Linked to original sources

[Clinical types of immunologic transplant reactions following perforating keratoplasty].

The incidence of allograft rejection was determined for 740 penetrating keratoplasties performed between 1980 and 1987. All 740 cases were followed up for at least 1 year. The reaction forms of allograft rejection were grouped according to biomicroscopic appearance. The incidence and progression of symptoms are described. Rejection types are subdivided into patients with favorable versus poor prognosis. Of the patients 37.9% demonstrated an immune response (including discrete forms). Clear reaction patterns within the two groups of patients became apparent when reaction variations were carefully differentiated. Epithelial immune reaction was found in 5.2%/10.5% and subepithelial infiltration in 1.7%/4.8% of the patients with favorable/poor prognosis. The largest disparity in frequency occurred in progressive endothelial reaction; 3.8% in patients with favorable versus 36.7% in patients with poor prognosis. Focal endothelial reactions occurred in both groups with comparable frequencies (14.1%/13.3%). The large percentage of immunological reactions, including late manifestations (approximately 12% after 1 year) and some with irreversible progression, warrants continuing efforts to treat and prevent this complication.

Cornea↗

Topical treatment of severe corneal ulcers with cyclosporin A.

Cyclosporin A eye drops were used on six patients to treat corneal ulcers associated with rheumatic diseases, oculomucocutaneous syndrome, and Sjögren's syndrome. Conjunctival excision was additionally carried out in two cases. All ulcers healed rapidly. The mechanism of ulcer formation involving T-lymphocytes is discussed.

Administration, Topical↗

[Bromocriptine: a new therapy concept in the treatment of chronic recurrent uveitis?].

Chronic recurrent uveitis still responds unsatisfactorily to therapy. Prolactin, a pituitary hormone that attains high blood levels physiologically in stress situations, has an immune modulating effect. The prolactin antagonist bromocriptine (2 x 2.5 mg/day) was administered prophylactically to prevent recurrence in seven patients with chronic iritis/iridocyclitis or panuveitis (Group A). On this therapy two patients suffered a mild recurrence (in one case in the first month). Another patient developed rebound uveitis after discontinuing bromocriptine medication. Tolerance appears to vary considerably, and in three patients the therapy had to be discontinued because of arterial hypotension and congestive rhinopathy, respectively. The three patients in Group B (with iritis, sympathetic ophthalmia, and intermediate uveitis) received bromocriptine in addition to cyclosporin A after plasmapheresis. This combination resulted in an elevated cyclosporin A plasma level, and the dosage was reduced by 30-50% (plasma level 70-120 ng/ml). With this lower dosage of cyclosporin A, the creatinine level of one of the patients returned to normal. Viewed on the basis of these initial results bromocriptine would appear to reduce the number of recurrences of chronic uveitis. Moreover, the synergism with cyclosporin A, described both theoretically and in an animal model in the literature, appears attainable in therapy.

Adult↗

[Nonspecific eye autoantibodies in uveitis].

Under certain pathologic circumstances autoantigens lead to the formation of autoantibodies. In uveitis, autoimmunologic phenomena will also be discussed. We studied 149 sera of uveitis patients for various organ specific and non-organ specific autoantibodies. We found antisarcolemal autoantibodies (ASA) mainly in patients with acute iritis (59% positive) but also in panuveitis (40%) and iridocyclitis (29%). On the other hand antiendothelial antibodies (AEA) could be found in 43% of patients with chorioretinitis. Antisinusoidal antibodies (SA) have been detected in iritis and panuveitis patients more often than in the control group which show positive autoantibodies in 5% of all cases. Using ELISA we looked for antibodies against keratin, laminin and microsomes. Because antimicrosomal-, antilaminin- and antisarcolemal-antibodies recognize the same epitope, there was a good correlation of these three autoantibodies. Similar clusters of autoantibodies (ASA, AEA and SA) have been found in various infectious diseases and in chronic inflammatory diseases in which an infectious component is discussed. These results may indicate that iritis, iridocyclitis, chorioretinitis and panuveitis are secondary reactions of eye tissue following a systemic primary disease. Especially viruses are well-known for their production of autoantibodies. In patients with intermediate uveitis we could not demonstrate these autoantibodies more often than in the control group, favouring theories which believe in an autoimmune reaction against vitreous elements.

Antibodies, Antinuclear↗

Retinal toxicity of liposome-incorporated and free ofloxacin after intravitreal injection in rabbit eyes.

BACKGROUND: Ofloxacin (OFLX) is a fluoroquinolone-antibiotic with a broad antimicrobial spectrum that may have a potential role in the treatment of bacterial endophthalmitis. However, its elimination half life after intravitreal injection is short. To prolong the intravitreal antibacterial level OFLX was incorporated into liposomes. This study was performed to investigate the retinal toxicity of liposome-incorporated and free OFLX. MATERIALS AND METHODS: OFLX was incorporated into multilamellar large vesicles. 0.1 ml of this suspension (= 180.2 microg OFLX) was injected into the midvitreous of rabbit eyes (n = 6). Free OFLX in doses of 100 microg, 500 microg and 1,000 microg was injected into the midvitreous of a second group of rabbit eyes (n = 18). The other eye served as a control and received empty liposomes or normal saline solution, respectively. Before injection and at the end of follow-up an ERG was obtained. After a follow-up of 1 day, 14 and 28 days the animals were perfused with glutaraldehyde and the eyes were examined by light- and transmission electron microscopy. RESULTS: The ERG as well as the histologic studies did not reveal any pathological changes after injection of liposome-incorporated OFLX compared to the control eyes. Significant reduction of the ERG was observed after 500 microg free OFLX in 2 out of 6 eyes after 1 and 14 days, respectively, and in 2 eyes 1 day after 1,000 microg free OFLX. Three days after injection of 1,000 microg OFLX the retina showed focal destruction in 1 out of 6 eyes. In another eye with the same dose 14 days after injection the photoreceptor outer segments showed disorganisation. CONCLUSION: This study shows that liposome-incorporated OFLX did not have any retinal toxicity in this animal model. Free OFLX appears to have no retinal toxicity in rabbit eyes at a dose of 100 microg after intravitreal injection. Injection of higher doses resulted in ERG changes and marked retinal damage.

Animals↗

Corneal allograft rejection: current understanding. I. Immunobiology and basic mechanisms.

Allograft rejection remains the single largest impediment to success in corneal transplantation. This article briefly reviews our current understanding of some fundamental aspects of corneal immunology and the pathogenetic mechanisms underlying corneal graft rejection. As knowledge increases, it is hoped that a better understanding of the immunobiology may result in improved preventive and therapeutic measures.

Cornea↗

Thalidomide inhibits leukocyte-endothelium interaction in endotoxin-induced uveitis.

To investigate the effects of thalidomide on leukocyte-endothelium interaction in iris vessels of rats with an endotoxin-induced uveitis (EIU), intravital fluorescence microscopy was used to quantify leukocyte adhesion to the vascular endothelium of iris venules in Lewis rats at 2, 4, 8 and 24 h after induction of EIU. Animals (n = 84) received a single intraperitoneal dose of either thalidomide (80 mg/kg body weight) or prednisolone (10 mg/kg body weight). Both drugs significantly reduced firm adhesion of leukocytes at 4, 8 and 24 h. Thalidomide caused earlier suppression of leukocyte rolling than prednisolone (4 vs. 8 h). TNF-alpha plasma levels peaked at 2 h and were not significantly reduced in any group compared with controls. Cell count and protein concentration in aqueous humor were significantly reduced by prednisolone and thalidomide at 24 h (p < 0.05). Thalidomide exerts its anti-inflammatory effects by an inhibition of leukocyte-endothelium interaction. Compared with prednisolone, thalidomide shows earlier inhibition of leukocyte rolling, indicating modulation of adhesion molecule expression and/or function.

Animals↗

Effects of a new immunotherapeutic agent (CG5601) on endotoxin-induced uveitis.

CG5601 is a novel immunomodulatory substance showing anti-inflammatory properties comparable to thalidomide. To investigate the anti-inflammatory effects of CG5601 in endotoxin-induced uveitis (EIU) and to evaluate its influence on leukocyte-endothelium interaction, the anterior chamber inflammatory reaction was assessed and intravital fluorescence microscopy was carried out at 2, 4, 8 and 24 h. Lewis rats received an intraperitoneal injection of CG5601 (200 mg/kg b.w.) at the time of lipopolysaccharide injection. At 8 and 24 h, CG5601 inhibited the cell migration and protein concentration in the aqueous humor compared to untreated EIU (p < 0.0001). There was no significant difference between nontreated animals and vehicle controls. The treatment of CG5601 reduced the number of rolling leukocytes. At early time points (2 and 4 h), inhibition of rolling leukocyte flux was significant (p < 0.005). The rise of serum TNF-alpha levels in EIU at 2 h was reduced. CG5601 exerts potent anti-inflammatory effects in EIU.

Animals↗

[Keratomalacia in rheumatoid arthritis: immunohistologic and enzyme histochemical studies].

Corneal and conjunctival biopsies of 13 patients with rheumatoid arthritis and corneal ulceration (RA-keratomalacia) have been characterized by immunohistological and histochemical analysis. Biopsies from 13 patients with bacterial conjunctivitis, 7 patients with allergic conjunctivitis, 15 patients with senile cataract and 15 patients with keratokonus served as controls. The phenotypic composition of the conjunctival inflammatory infiltration of rheumatoid corneal ulceration was not significantly different from the other inflammatory eye diseases studied. However, conjunctival epithelial cells of all RA-patients showed strong de novo expression of HLA-DR- and DP-antigens. HLA-DQ-antigens were only weakly expressed in a minority of patients. In bacterial conjunctivitis a less intense HLA-class-II-expression was found to be restricted to HLA-DR-antigens. Furthermore, in RA patients stromal fibroblasts of the cornea expressed lysosomal elastase. Both observations could be explained by paracrine action of interleukins produced by infiltrating T-lymphocytes and macrophages. Thus, it might be tempting to speculate that immunologically induced, elastase mediated autodegradation of corneal stroma may be an important factor in the pathogenesis of rheumatoid corneal ulceration.

Antigens, Differentiation, T-Lymphocyte↗

Complement-derived anaphylatoxins in human donor corneas treated with excimer laser.

BACKGROUND AND OBJECTIVE: An inflammatory response produced by excimer laser photorefractive keratectomy (PRK) may be associated with the subsequent corneal haze and regressions in refractive error observed after treatment. Complement-derived anaphylatoxins, potent mediators of inflammation, may have a role in postoperative healing. MATERIALS AND METHODS: Twenty right human donor corneas underwent a 6-D excimer laser PRK treatment. The corresponding left donor corneas served as the controls. After incubation in tissue culture media for 6 hours and elution in phosphate-buffered saline with EDTA for 24 hours, complement-derived anaphylatoxins C3a, C4a, and C5a were measured in corneal eluates by radioimmunoassay. RESULTS: Compared with control corneas, the excimer PRK corneas failed to demonstrate a significant increase in C3a, C4a, or C5a levels (P > .05). CONCLUSIONS: These results suggest that the excimer laser at this dose does not activate significant complement in the cornea.

Adolescent↗