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Biomedical subjects

A Kijlstra

Publications and source records attributed to A Kijlstra.

At least 109 records · Page 6Linked to original sources

N-acetyl-aspartyl glutamic acid (NAAGA) topical eyedrops in the treatment of giant papillary conjunctivitis (GPC).

Giant Papillary Conjunctivitis (GPC) is a conjunctival inflammatory condition associated with contact lens wear. The etiology is still unknown and no adequate treatment is found. Mastcell stabilizing drugs are useful in the treatment of chronic inflammatory processes. The effect of 6% N-acetyl-aspartyl glutamic acid (NAAGA), a mastcell stabilizing agent, in a double-masked comparative trial with placebo in the treatment of GPC is reported. Seventeen patients with symptomatic GPC were treated over a four week period, eyes were randomized to receive NAAGA or placebo. A decrease in symptoms was found for both eyes. No significant difference of clinical symptoms and signs were observed between NAAGA or placebo treated eyes. These results suggest a wash effect of placebo in GPC. Tear C3a showed a increased level compared to normals but no statistically significance was observed in our study. The results of this study indicate that mastcell stabilization in GPC has little effect and treatment should be focused more on inflammatory mediators released because of mechanical stimuli.

Administration, Topical↗

Analysis of corneal aldehyde dehydrogenase patterns in pathologic corneas.

In this study we investigated the properties of corneal aldehyde dehydrogenase (ALDH) in keratoconus corneas using various electrophoretic techniques combined with immunochemical and zymographic identification. Normal corneas and other pathologic corneal buttons obtained during keratoplastic surgery were used as a control. A significant (p < 0.001) lower enzymatic activity was found in keratoconus epithelial extracts (3.1 +/- 2.1 IU/mg protein) compared with normal controls (5.5 +/- 2.6 IU/mg protein), whereas no significant differences were observed in the stromal and endothelial extracts. No significant differences were observed for the corneal ALDH thermolability behavior, nor did any marked changes occur in the position of the 54- and 88-kDa species when comparing the pathologic corneas and normal controls. On the other hand, isoelectric focusing analysis showed a different pattern for the pathologic corneas as compared with controls. Moreover, native-polyacrylamide gel electrophoresis analysis showed that normal corneas exhibit three bands, whereas keratoconus and other pathologic corneas only show two bands. The shift from the three-band pattern to the two-band pattern could be reproduced in vitro using reducing agents, such as glutathione.

Adolescent↗

Neutrophil activation in ivermectin-treated onchocerciasis patients.

Ivermectin is a safe and effective drug for onchocerciasis treatment. In certain individuals, however, therapy is accompanied by adverse reactions. The mechanisms underlying these reactions are not yet known. The aim of the present study was to investigate whether neutrophils are involved in the development of these adverse reactions. Elastase and lactoferrin, two markers for the release of neutrophil azurophilic and specific granule contents respectively, were measured by radioimmunoassays in plasma of onchocerciasis patients with varying degrees of side effects, as well as in control subjects before and 1 and 2 days after ivermectin treatment. A considerable increase of elastase levels after treatment was observed, whereas lactoferrin levels did not change. The percentage of patients with elevated elastase levels was significantly correlated with the degree of side effects. These findings suggest that neutrophil activation may be involved in the development of adverse reactions in these patients.

Cell Degranulation↗

Does autoimmunity to S-antigen play a role in Fuchs' heterochromic cyclitis?

Autoimmunity directed against retinal or choroidal antigens has been suggested to play a role in the chorioretinal lesions observed in patients with Fuchs' heterochromic cyclitis. This hypothesis was addressed and patients with Fuchs' heterochromic cyclitis were tested for cellular immunity (migration inhibitory factor assay) against human retinal S-antigen. A significantly higher percentage of patients with Fuchs' heterochromic cyclitis had a positive cellular autoimmune response to S-antigen than healthy controls and other patients with anterior uveitis. This finding is remarkable since Fuchs' heterochromic cyclitis is generally classified as an anterior uveitis and patients with Fuchs' heterochromic cyclitis without chorioretinal lesions also had a positive test. In view of these results and a sensitisation against a corneal antigen reported earlier in Fuchs' heterochromic cyclitis, it is suggested that a chronic low grade grade anterior uveitis or chorioretinitis of unknown origin may cause the release of potent autoantigens in these patients.

Adult↗

Concurrent parasitic infections in onchocerciasis and the occurrence of adverse reactions after ivermectin treatment.

Ivermectin is a safe, effective, and relatively well-tolerated drug for the treatment of human onchocerciasis. However, due to side effects of the drug, large-scale ivermectin distribution without medical supervision is not recommended. The mechanisms involved in the pathogenesis of ivermectin-induced adverse reactions are not yet known. Since onchocerciasis patients are likely to have concurrent parasitic infections, we investigated whether side effects that occur after ivermectin treatment could be related to the presence of parasite eggs and cysts in stool samples prior to treatment. One hundred twenty-nine onchocerciasis patients were treated with a single dose of ivermectin (150 micrograms/kg) and side effects were graded according to the classification of Greene and others. Stool samples were collected before and three days after treatment. A high percentage (80.5%) of the patients reported adverse effects (57% mild, 14.1% moderate, and 9.4% severe reactions). Most (95.1%) of the patients had one or more concurrent parasitic infections. No relationship could be found between the occurrence and extent of side effects and the severity of concurrent intestinal parasitic infections. However, side effects were significantly correlated with pretreatment microfilarial counts. Ivermectin treatment did not induce significant short-term changes in Trichuris trichiura or Schistosoma mansoni egg counts. However, a significant reduction in Ascaris lumbricoides egg counts and Entamoeba coli cyst loads was observed; a cure rate of 46% for cysts was reached. In contrast, hookworm egg production increased after ivermectin treatment. Further studies are required to verify ivermectin-induced changes in cyst and hookworm loads as well as the significance of these findings.

Animals↗

Chemoattractant and neutrophil degranulation activities related to interleukin-8 in vitreous fluid in uveitis and vitreoretinal disorders.

PURPOSE: To investigate whether the cytokine interleukin-8 (IL-8), a strong chemoattractant and activator for neutrophils, is responsible for neutrophil infiltration and degranulation in the eye in uveitis. METHODS: IL-8 and elastase were measured with specific enzyme-linked immunoassays in vitreous fluid samples obtained from 69 patients with various uveitis entities. Vitreous fluid of nonuveitis patients and eye bank eyes served as controls. The chemotactic activity of vitreous fluid was tested with the Boyden chamber technique. RESULTS: IL-8 was detected in 45% of the vitreous fluid samples from uveitis patients and in 26% of vitreous fluid samples from nonuveitis patients. Vitreous fluid samples with IL-8 levels exceeding 100 pg/ml were chemotactic for neutrophils. This chemotactic activity could be blocked by 41% to 79% with a monoclonal anti-IL-8 antibody. Elastase levels in vitreous fluid of uveitis patients with detectable IL-8 were significantly higher than those in vitreous fluid samples with no detectable IL-8. CONCLUSION: These results indicate that IL-8 participates in the inflammatory processes in the eye by attracting and degranulating neutrophils. It is suggested that these processes contribute to the pathogenesis of tissue destruction in uveitis.

Cell Degranulation↗

Quantitative analysis of iris translucency in Fuchs' heterochromic cyclitis.

PURPOSE: To measure intraocular stray light and to quantify translucency of the iris and the surrounding ocular wall in both eyes of patients with Fuchs' heterochromic cyclitis; to investigate whether differences in paired eyes could be measured in patients without heterochromia or with a minimal degree of iris atrophy. METHODS: Intraocular stray light was measured by means of the direct compensation technique. A modification of this technique was used to quantify translucency of the iris and the surrounding ocular wall. RESULTS: Intraocular stray light proved to be significantly higher in all patients with Fuchs' heterochromic cyclitis (both eyes) than in normal control subjects. Translucency of the iris and the ocular wall around it were increased in the patients with Fuchs' heterochromic cyclitis, including patients without heterochromia or with a minimal degree of iris atrophy. CONCLUSIONS: Quantitative analysis of translucency was used to determine iris depigmentation in vivo in patients with Fuchs' heterochromic cyclitis. This technique showed that the process of atrophy and depigmentation in patients with Fuchs' heterochromic cyclitis is probably not restricted to the iris, but also occurs in the surrounding ocular wall. More studies, including other uveitis groups, are necessary to investigate if this technique can be used as a diagnostic tool in Fuchs' heterochromic cyclitis.

Adult↗

Scleral flap sutures and the development of shallow or flat anterior chamber after trabeculectomy.

To determine whether closing the scleral flap with extra sutures can reduce the risk of overfiltration after trabeculectomy, we divided 339 trabeculectomies into three groups based on the number of scleral flap sutures used in the procedure, and studied the postoperative complications and results. The incidence of shallow or flat anterior chamber was significantly less in eyes that had received seven to nine sutures than in those that had received from two to six. Also, the incidence of cornea-lens touch was significantly less in the eyes with seven to nine sutures (P = .02, Fisher Exact Test). This study suggests that extra scleral flap sutures (in combination with laser suture lysis) is a safe and effective method of significantly reducing the risk of overfiltration after trabeculectomy.

Adolescent↗

Immune deposits in iris biopsy specimens from patients with Fuchs' heterochromic iridocyclitis.

To investigate whether Fuchs' heterochromic iridocyclitis may be an immune complex vasculitis, we used an immunofluorescence technique to detect immunoglobulins and complement in iris biopsy specimens from nine patients with Fuchs' heterochromic iridocyclitis, 12 patients with other types of uveitis, and nine patients with glaucoma but without uveitis. No specific immune deposits were observed in the irises of the patients with Fuchs' heterochromic iridocyclitis. Immunoglobulin G, IgA, IgM, and complement were detected in patients with Fuchs' heterochromic iridocyclitis and patients with uveitis, and these results differed significantly (P less than .05) from the group without uveitis. The immune deposits were found only in the iris vessel walls. No light-microscopic evidence of an inflammatory vascular process could be detected. Further studies are necessary to investigate whether the immune reactants originate from the circulation or result from local formation.

Adult↗

Fuchs' heterochromic iridocyclitis is not associated with ocular toxoplasmosis.

To analyze the association between Fuchs' heterochromic iridocyclitis (FHI) and toxoplasmosis, we performed ocular examinations and used various specific laboratory tests to establish a role for Toxoplasma gondii in the pathogenesis of FHI. Results were compared with those for other types of uveitis and healthy controls. Of the 88 patients with FHI, nine (10.2%) had toxoplasmosislike scars, but an association could not be proved by the indirect immunofluorescence antibody test or enzyme-linked immunosorbent assay, or by a test for cellular immunity to Toxoplasma antigen. Analysis of aqueous humor samples for Toxoplasma antibodies in patients with FHI also yielded negative results. On the basis of the negative results of these laboratory tests, we concluded that FHI is not associated with ocular toxoplasmosis.

Adolescent↗

Analysis of the electroretinogram in toxoplasma retinochorioiditis.

The decision to use therapy in toxoplasma retinochorioiditis depends on the location of the active lesion and the presence of vitreous activity. In eyes with dense vitreous clouding it can be difficult to see whether the macular region is involved or not. In theory the localisation of a lesion can be estimated on the basis of the flash ERG. The standard flash electroretinogram was recorded in 23 patients with inactive toxoplasma retinochorioiditis lesions in the retina. In 17 cases a lesion was present within the central 12 degrees of the visual field, 8 of these had a reduced photopic ERG. In 15 patients lesions were found outside the central 12 degrees, in 8 of whom the scotopic ERG was reduced. We conclude that the ERG can be of use in indicating the scar location in patients with dense vitreous clouding.

Adolescent↗

Anti-retinal S-antigen antibodies in human sera: a comparison of reactivity in ELISA with human or bovine S-antigen.

Various studies have demonstrated anti-retinal S-antigen (S-ag) antibodies in uveitis sera in assays using bovine S-ag. Because of its molecular similarity and cross-reactivity with human S-ag, reactions with bovine S-ag have been considered a reliable indication of anti-S-ag autoimmunity. To test this assumption, the cross-reactivity of purified human and bovine S-ags was quantitated by ELISA titration of various anti-human and anti-bovine S-ag immune reagents raised in mice, rats and rabbits. Anti-human S-ag reagents appeared to be largely cross-reactive with bovine S-ag, whereas anti-bovine S-ag reagents were 6-10 times less reactive with the cross-reacting human S-ag than with bovine S-ag, thus showing a predominant role of species-specific epitopes on bovine S-ag. Furthermore, a large number of human control and uveitis sera was tested in ELISA with both human S-ag- and bovine S-ag-coated microwells. Both the numbers of positive sera and the levels of anti-S-ag antibodies in the two tests significantly correlated, but many exceptions were found, and the predictive value of reactions with bovine S-ag for the presence and levels of anti-S-ag autoantibodies was low. For individual human sera, assessment of anti-S-ag autoantibodies requires the use of human S-ag in immunoassays.

Animals↗

Analysis of aqueous humour in uveitis by high performance liquid chromatography and sodium dodecyl sulphate-polyacrylamide gel electrophoresis.

Aqueous humour from patients with Fuchs' heterochromic cyclitis (FHC) and other types of uveitis was analysed by high performance liquid chromatography (HPLC) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Using HPLC, the number of peaks and their respective elution times were similar for the FHC, uveitis and control groups. SDS-PAGE and silver staining showed immunoglobulin G migrating as two to four distinct bands in all non-reduced samples. In the reduced state, 1-5 unidentified low MW bands (10-19 kD) were seen. Two bands at 19 and 10 kD appeared to be specific for the uveitis group, and a band at 11 kD was present in 76% of uveitis and 19% of FHC patients. None of these three bands were detected in any of the control group. As yet the identity of these low MW proteins and their possible significance in the pathogenesis of intraocular inflammation are unknown.

Adult↗

Isoelectric focusing pattern of human corneal aldehyde dehydrogenase.

The major soluble protein in the bovine cornea (BCP 54) has recently been identified as a class 3 aldehyde dehydrogenase. An enzymatic and even a possible structural role of this protein in the mammalian cornea has been proposed. Earlier we showed that the human cornea contains the same enzyme but with a different substrate specificity, compared to the bovine. Moreover, the enzymatic activity was harbored in the dimeric 88-kD species. Genetic variants have been found for several mammalian ocular aldehyde dehydrogenases. In this study we investigated whether such variants were also present in the human cornea by using a zymography technique for aldehyde dehydrogenase activity and immunoblotting with rabbit anti-BCP 54 and lectin staining after isoelectric focusing (IEF) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We investigated 50 individual human corneal epithelial extracts and found one common IEF variant (n = 47) and two "rare" IEF variants in three individuals. Analysis of these patterns indicates that the observed IEF profiles may be caused by posttranslational events.

Adolescent↗

Fluorophotometric assessment of tear turnover under rigid contact lenses.

To examine the effect of rigid contact lens design on tear turnover the left and right eyes of 25 healthy volunteers were randomly fitted with either a spherical or an aspherical contact lens. Tear turnover is defined as the percentage of decrease of fluorescein concentration in the tear film per minute as a result of tear flow after instillation of fluorescein and can be determined with a fluorophotometer. A drop of fluorescein (1 microliter, 2%) was instilled in each contact lens-wearing eye, whereafter the decrease of the fluorescein was measured for about 30 min. The test was repeated without contact lenses. No statistically significant difference was found between the tear turnover in the spherical, the aspherical, and the non-contact lens-wearing eyes (mean values +/- SD: 15.2 +/- 4.9, 15.6 +/- 5.9, and 16.9 +/- 6.8%/min, p > 0.20).

Adult↗