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Enhancing effects of fluorescein on beta-lactam rash. II: Enhancing effects of fluorescein on generalized rash induced by beta-lactam antibiotics in guinea pigs.

Healthy volunteers, who were receiving intravenous injections of cefclidin (CFCL) with frequent concomitant use of fluorescein (F) and oxybuprocain (O) in the eyes for measurement of ocular tension, developed drug eruptions at the high frequency of 66.7%. The injection of CFCL alone induced the eruptions at an incidence of 2.8%. The cause of this high eruption rate was thought to be the simultaneous treatment with F and/or O. Therefore, we conducted experiments with CFCL-induced generalized rash (GR) in guinea pigs. Guinea pigs treated with F and O during both the phases of immunization and intraperitoneal elicitation developed CFCL rashes at a high frequency. This CFCL-rash was augmented by the treatment with F during either phase, but not by the treatment with O. Skin testing induced delayed type hypersensitivity (DTH) reaction to O in some animals, but the DTH to F was not induced in animals immunized with F in complete Freund's adjuvant. Furthermore, F augmented rashes induced not only by CFCL but also by other beta-lactam antibiotics such as cefsulodin and sulbenicillin. Accordingly, it is likely that F played a dominant role in the high incidence of drug eruptions during the volunteer trials with measurement of ocular tension.

Animals↗

The normal fundus fluorescein angiogram. III. A longitudinal fluorescein angiographic study of the fundus in insulin dependent diabetics without ophthalmoscopically abnormalities.

In 17 insulin dependent diabetics with an apparently normal ophthalmoscopy at the entry of the study, there was a) an individual variation regarding observed fundus elements and b) an intraindividual variation during the observation time of one year, as evident from fundus fluorescein angiography, colour photography and red free filter photography. The examinations were performed on one eye in each subject three times within one year. Hyperfluorescent elements--varying in number from 1 to 5--were found totally in 14 eyes (= 82%). In 6 eyes (= 35%) the number of minute hyperfluorescent fundus elements varied during one year. Hypofluorescent elements were present in 14 eyes (12 eyes with indistinctly and and 2 with distinctly outlined elements) and showed no variation during one year. Eleven eyes (65%) had minute elements--varying in number from 1 to 7--in the colour and red free filter photographs not visualized in the angiograms. After one year 8 red elements were found in 5 eyes, 6 with and 2 without fluorescence. The remaining fluorescent and non-fluorescent elements, constantly present, appeared as minute yellowish spots (n = 37).

Adult↗

Fluorescein angiography in inflammation of the peripheral fundus: the normal fluorescein angiographic pattern. I.

The normal angiographic pattern of the peripheral vasculature was studied in 25 healthy individuals. There was no pathologic leakage of dye from the choroid or retina. However, small areas of choroidal nonperfusion occurred even in young persons. Vessels which never filled with fluorescein represented a common feature of the peripheral retinal vasculature. As a rule, pars plana corporis ciliaris did not stain with dye during the whole angiogram.

Adolescent↗

Peroxidase and fluorescein isothiocyanate as antibody markers. A quantitative comparison of two peroxidase conjugates prepared with glutaraldehyde or periodate anda fluorescein conjugate.

Batches of rabbit anti-human immunoglobulin G antibodies were labeled either with horseradish peroxidase, using the two-step glutaraldehyde method or the periodate method, or with fluorescein isothiocyanate (FITC). The peroxidase conjugates were isolated by chromatography using two different gel types. The five types of conjugates thus obtained were standardized to the same amount of rabbit immunoglobulin G. The antibody activity, as estimated by means of single radial immunodiffusion and passive hemagglutination, and the enzyme activity, determined with orthodianisidine, were compared. The ultimate dilutions and absolute amounts of the five conjugates giving positive reactions were determined in direct and indirect immunohistochemical tests, using both cryostat sections of skin and the agarose bead model system. It appeared that during the peroxidase conjugation procedures there was a considerable loss of abtibody and enzyme activity, whereas in the FITC conjugation procedure the antibody activity remained intact. Neverthe less, peroxidase conjugates prepared with glutaraldehyde still gave positive staining reactions in equal or somewhat higher dilutions than the fluorescin conjugate did. The peroxidase conjugates prepared with periodate could not be diluted to the same extent. For the detection of antibodies by indirect immunohistochemical methods, the peroxidase conjugate, prepared with glutaraldehyde, was comparable to the FITC conjugate. The peroxidase conjugate, prepared with periodate, was less effective.

Aldehydes↗

The normal fundus fluorescein angiogram. II. A longitudinal fluorescein angiographic study of the fundus in clinically healthy subjects without ophthalmoscopically abnormalities.

Three consecutive photographic fundus examinations using colour, interference filter photographs and fluorescein angiography showed no intraindividual variation within one year, but a considerable interindividual variation of the morphologic fundus elements was found in 48 eyes of 48 clinically healthy middle aged subjects. There were 20 eyes with distinctly outlined minute hyperfluorescent elements, 15 eyes with minute indistinctly outlined and 3 eyes with distinctly outlined hypofluorescent elements. These elements remained unchanged after one year. In 80% of the eyes with hypofluorescent elements there were characteristically no concomitant hyperfluorescent elements. Seventeen of 48 eyes had fundus elements exclusively visible in the colour and filter pictures. Most hyperfluorescent elements corresponded with elements in the green interference filter photographs (85% of the eyes). These findings indicate minute changes in the layers of Bruch's membrane and the retinal pigment epithelium in most of the eyes. The indistinctly outlined hypofluorescent elements might represent minute choroidal vascular filling defects or minute areas with blockage of the choroidal fluorescence.

Fluorescein Angiography↗

Soluble oligovalent antigen-antibody complexes. I. The effect of antigen valence and combining ratio on the composition of fluorescein-carrier anti-fluorescein complexes.

Soluble oligovalent antigen--antibody complexes were prepared and analysed by ultracentrifugation in order to study the effect of the combining ratio, antigen valence and concentration upon the size and molecular composition of the composition of the complexes. Fluorescein (F) conjugates of rabbit serum albumin (RSA) and thyroglobulin (RTg) were combined with high affinity rabbit anti-F antibodies to form soluble complexes. The effect of the combining ratio paralleled findings in precipitating systems in that the largest soluble complexes were found at equimolarity and mild molar antibody excess. Tetravalent antigen formed precipitates at combining ratios near equimolarity, whereas trivalent antigens failed to precipitate at similar concentrations. Complexes prepared near equimolarity were most sensitive to changes in concentration, higher concentrations leading to larger complexes. The Ab/Ag ratios of different-size complexes in the same preparation were remarkably similar. This ratio was dependent on the antibody--antigen combining ratio, was limited by antigen valence and was not affected by concentration differences. The data support the hypothesis that soluble complexes are formed in two steps. First, antigen and antibody combine to form subunits whose Ab/Ag ratio is determined by the combining ratio and antigen valence. These subunits then combine to form larger complexes in a manner analogous to polymerization.

Antibodies↗