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Biomedical subjects

G Duncker

Publications and source records attributed to G Duncker.

At least 55 records · Page 3Linked to original sources

Chlorphentermine-induced lipidosis in the rat retina: a functional and morphological study.

Chronic administration of the cationic amphiphilic anorexigenic drug chlorphentermine to rats has previously been shown to induce extraocular and ocular lipidosis: large numbers of lipidosis-related cytoplasmic inclusions can be found in the pigment epithelium and smaller numbers in the neuroretina. In the present study, female albino Wistar rats were treated orally with chlorphentermine (30-45 mg/kg body weight) for 4-16 weeks. The animals were submitted to electroretinography, and the retinae were prepared for histological investigations. Our histological findings corresponded to previous reports. The changes in electroretinographic parameters were low. The clearest change was a reduction of the b-wave amplitude of 20% after 12 and 16 weeks of treatment compared with the values before drug treatment. The a-wave amplitude did not differ from that in the control group. Lipidosis in the neuroretina may be the reason for functional influences on the b-wave amplitude. The function of the receptor cells, which is represented by the a-wave, appeared unaffected by chlorphentermine.

Administration, Oral↗

A new system for recording electroretinographical potentials in animals.

Electroretinography can provide meaningful evidence of oculotoxic changes. We describe a new recording system specially constructed for animal experiments. It meets the standards for electroretinographical investigations and recording systems set up by international committees. The recording apparatus has a resolution of 0.49 microV (amplitude) and 1 ms with a sensitivity range of +/- 1 mV full scale and a band-pass of 0.03 to 1,000 Hz. The signals are digitized and processed by a computer. The calibration symbol is faithfully represented as a rectangular impulse with an amplitude of 100 microV and a period of 100 ms. Normal values were calculated for 25-week-old albino Wistar rats. The normal range is defined as the mean +/- 2 SD for A and B wave parameters. These normal values can serve as reference values for future studies in oculotoxicity.

Animals↗

ANCA in ocular inflammatory disorders.

400 patients presenting with active inflammation of the conjunctiva, sclera, orbita, uvea or retina were cANCA negative during active disease, however, pANCA were found in 15%. Another group of 100 patients suffering from Wegener's granulomatosis (WG) showed in 72 cases one or multiple ocular inflammatory symptoms. They were frequently cANCA-positive. Contrary to some other reports dealing with ocular inflammation, we find a high specificity of cANCA for Wegener's granulomatosis and, therefore, recommend cANCA-testing in all ocular inflammatory disorders, which may be difficult to differentiate from a manifestation of WG.

Antibodies, Antineutrophil Cytoplasmic↗

Orbital involvement in Wegener's granulomatosis.

Orbital granulomas may complicate the course of Wegener's granulomatosis (WG). Granulomas that grow and compress the optic nerve may lead to blindness. Careful magnetic resonance imaging (MRI) is recommended for early detection and follow-up of intraorbital granulomas. Sufficient systemic immunosuppressive treatment should be given as usual for Wegener's granulomatosis. In order to preserve vision orbital decompression may be necessary in rapidly progressive pseudotumor of the orbit.

Adult↗

MRI of the head in Wegener's granulomatosis.

MRI of the head was performed in 25 patients suffering from Wegener's granulomatosis. 23 patients showed mucosal inflammation in the nasal cavity and in the paranasal sinuses, 10 patients had granulomas in the paranasal sinuses and in the orbits, 7 patients had cerebral lesions, 3 patients had submucosal hemorrhages in the paranasal sinuses and 3 patients showed bone erosions or destructions in the facial skeleton, which was visible only by CT.

Bone and Bones↗

Adhesion molecules in normal human conjunctiva. An immunohistological study using monoclonal antibodies.

In this immunohistochemical light microscopic study we applied a panel of monoclonal antibodies to study the expression pattern of adhesion molecules in normal human conjunctiva from 15 patients. The molecules we analyzed included the VLA-family VLA-1-6, the leukocyte integrins LFA-1, Mac-1 and p150,95, the immunoglobulins LFA-3, CD2, ICAM-1 and VCAM-1 and the selectin ELAM-1. Our results show that only VLA-2, VLA-3, LFA-3, and the VLA-alpha 6 subunit are expressed on the epithelium. A strongly basal accentuation of the VLA-alpha 6 subunit indicates its possible relevance in anchoring the epithelium at the substantia propria. Intraepithelial T cells were VLA-1, VLA-5, LFA-1, and CD2 positive. Endothelial cells expressed VLA-1, VLA-2, VLA-3, VLA-5, VLA-alpha 6, ICAM-1, and LFA-3. ELAM-1 was seen only in specimens from five patients. Interestingly, mast cells were positive for VLA-3 and VLA-5, both of which are receptors for fibronectin, indicating that these integrins play an important role in mast cell function. Our study builds the basis for further investigations in adhesion molecules in conjunctival diseases.

Adolescent↗

Comparison between the flicker test procedures of Aulhorn and of Dölle in the diagnosis of optic neuritis.

The use of the flicker test for diagnostic purposes is based on the absence of Brücke's effect during acute inflammation of the optic nerve. The test device of Aulhorn was compared with another, less expensive flicker test device, that of Dölle. The flicker test device of Aulhorn uses a mechanical projection system. In the device of Dölle, the flicker field is formed by electronically controlled groups of light-emitting diodes. In an initial examination, the reliability of Aulhorn's test was slightly higher than of Dölle's procedure. The normal ranges in 45 healthy subjects differed markedly between the two methods. One hundred and fifteen eyes of patients with established or suspected optic neuritis were also examined. Although there were differences in some conditions (e.g. shape and homogeneity of flicker field) due to the techniques, the specificity and sensitivity of the two methods were similar concerning the diagnosis of acute optic neuritis.

Acute Disease↗

[HLA typing in high risk keratoplasty].

UNLABELLED: Improved microsurgical techniques and better immunosuppressive treatment have led to an increase in the number of corneal transplantations. However, graft rejection due to a disparity between donor and recipient major histocompatibility antigens remains the major complication. The risk of graft rejection is further increased in patients with vascularized graft beds and in presensitized persons. Well-designed experimental studies and clinical experience have clearly shown the importance of class-I-antigens. However, class-II antigens have not yet been studied to the same extent. METHODS: Multiorgan donors and corneal graft recipients were HLA typed using the lymphocytotoxicity test previously described by Terasaki. The recipients were typed retrospectively. Cadaver corneal graft donors were typed using a novel HLA typing technique on retinal pigment epithelial cells, as previously described by us. Postoperatively, all recipients were routinely examined for rejection over a period of 2 years. RESULTS: Graft rejection was observed in 25% of the 133 high-risk patients. Of the 13 class-I-typed patients who showed a rejection 9 persons had two or more major histocompatibility mismatches. Of the 12 patients without rejection problems only 5 had two or more HLA class-I-mismatches. Of the patients with one or two matches at the HLA-DR locus there were only 4 out of 9 patients with at least one graft rejection; 5 out of 6 patients showed no signs of rejection. CONCLUSIONS: Mismatches at either class-I- or class-II- gene loci lead to a higher frequency in corneal graft rejection. Apart from the major histocompatibility mismatches, other factors also influence graft rejection, such as the distance between the corneal transplant and corneal vessels, presensitization, and the indication for corneal grafting. If we are to define the factors influencing graft rejection better and further increase our knowledge on the role the major histocompatibility antigens play in corneal graft rejection in a larger patient group, then cooperation with other transplantation centers will be required.

Graft Rejection↗

[The magnetic resonance tomographic signs of Wegener's granulomatosis in the head area].

MRI of the head was performed in 25 patients suffering from Wegener's granuloma. 23 patients showed evidence of mucosal thickening in the paranasal sinuses, the middle and inner ears and in the mastoid cells; these were characterised by low signal intensity of T1-weighted and high signal intensity of T2-weighted images. In 10 patients there were granulomas in the paranasal sinuses and in the orbits which showed low signal intensity of both T1-weighted and T2-weighted images. In 4 patients, additional images were obtained after the intravenous injection of Gd-DTPA. In 2 patients this resulted in non-homogeneous contrast accumulation in the granuloma. In 7 patients there were signal changes in the brain which were typical of infarcts. The complete extent of bone destruction in the facial skeleton was visible only by CT.

Adult↗

[Orbital involvement in Wegener's granulomatosis].

BACKGROUND: Granulomas of the orbit can complicate Wegener's granulomatosis (WG). If they compress the optic nerve, blindness of one or both eyes may result. Therefore, early detection and sufficient treatment are important. MATERIAL AND METHODS: Computed tomography (CT) and magnetic resonance imaging (MRI) of the orbit and CNS were performed in patients suffering from WG and orbital granulomas (n = 6). The patients were seen interdisciplinary by internists, ENT-specialists, radiologists and ophthalmologists. RESULTS: 12 out of 121 biopsy proven WG-patients showed orbital granulomas during their disease process. Granulomas of the orbit could be best visualized by MRI. However, MRI and CT taken together were most informative. 6 patients with orbital granulomas are presented as case reports, in four of them WG lead to blindness of one eye. The course of orbital granulomas may be chronic progressive or acutely fulminant. Therapy of first choice is a high dosage, long-term immunosuppression with cyclophosphamide and prednisolone. CONCLUSIONS: The detection of orbital granulomas in WG is most successful using CT and MRI. In addition to that, the analysis of visual acuity and visual field are the most important parameters in the detection and follow-up of orbital granulomas. A high dosage, long-term immunosuppression is the treatment of first choice, but in rapidly progressive cases an early decompression of the orbit has to be discussed additionally.

Abscess↗

Post-mortem HLA tissue typing of retinal pigment epithelial cells.

Retinal pigment epithelial cells (RPE) were derived from bulbi of cornea donors and maintained in culture. The time-span between donor's death and cell cultivation ranged from 2 to 122 h. The mean numbers of hours was 25.6 (n = 130). After IFN-gamma stimulation, cells were serologically typed for class I and class II antigens. Unclear class I allospecificities were verified by one-dimensional isoelectric focusing. Data from the serological typing of lymphocytes and those of the serological and biochemical typing of RPE from the same donors were compared in 22 cases. There was a discrepancy of less than 5%, whereby either the typing on lymphocytes could not identify some specificities declared as blanks or the RPE typing had failed to clearly define a specificity. Our data show that the strategy adopted here is very successful for tissue typing post mortem, thus increasing the number of available HLA-matched corneas and consequently reducing the number of corneal graft rejections.

Adolescent↗

Expression of MHC class I and II molecules by cadaver retinal pigment epithelium cells: optimization of post-mortem HLA typing.

The objective of this study was to investigate the expression of MHC antigens by retinal pigment epithelium cells (RPE) after stimulation with interferon-gamma (IFN-gamma) and to improve the currently practised technique of cadaver HLA typing. A concentration of 100 U/ml IFN-gamma induced expression of class I molecules up to greater than 90% 3 days after stimulation, whereas 50 U/ml were required for the expression of HLA-DR to greater than 90%. A concentration of 750 U/ml induced 35-45% expression of HLA-DP and less than 25% HLA-DQ after 3 days. Cells were serologically typed using the standard lymphocytotoxicity assay 3 days after stimulation with 250 U/ml IFN-gamma. Typing of class I specificities was complemented by one-dimensional isoelectric focusing (1D-IEF). We observed high concordance between the results of the RPE typing and the lymphocytotoxicity test on the same donors. Our results show complete typing of class I and II antigens post-mortem, which, in particular, enables graft matching and improvement of graft survival in recipients of organs removed many hours after death such as the cornea.

Adolescent↗

[Mass screening of blue color vision in divers with the desaturated Lanthony-15-Hue Test].

We tested 1002 persons, 572 divers (including 38 who had diving accidents) and 430 nondivers, for defects of the blue-sensitive system during the years 1988 and 1989. Recent research has shown functional disorders of color vision in divers, linked to previously described alterations of the retinal capillary system and pigment epithelium. The desaturated Lanthony-15-HUE test was used as a screening method. No defect of the blue-sensitive system was found, either in divers or in nondivers. Our results are similar to those of other researchers. One exception was that we found no correlation between age and error score. We found no evidence for retinal damage caused by diving.

Adult↗

[Relevance of ocular pressure tonometry and classical tonometry with reference to prognosis in suspected glaucoma and ocular hypertension].

A total of 44 eyes of patients with suspected glaucoma or ocular hypertension were examined both by ocular pressure tonometry (OPT) according to Ulrich and by tonography according to Leydhecker. The visual fields of these eyes were prospectively followed up for 3 years to compare the prognostic value of the two methods. In 30 of the 44 eyes a worsening visual field loss was observed, while in 14 the visual fields showed no change. Much better correlation was noted between values obtained by OPT and changes in visual field than between values obtained by tonography and visual field loss. Conventional tonography yielded 39% of false-negative values, but only 11% were recorded with OPT. Therefore, according to results of these and further investigations, OPT appears to be a more helpful and reliable method for assessment and decisions on therapy in patients with suspected glaucoma or ocular hypertension.

Humans↗

[Postmortem serologic and biochemical HLA typing with cultivated retinal pigment epithelium cells].

A quick and reliable method for HLA typing of human cadavers has been established. Retinal pigment epithelial cells (RPE) were obtained from cadaver bulbi 8-36 h post mortem (n = 24). After 24 hours, cell growth correlated inversely with the time lapse between the donor's death and bulbus explantation. Cultivated human RPE were stimulated by different Y-interferon (IFN) concentrations and examined by FACS analysis for the expression of MHC class I and II molecules. A concentration of 100 units/ml human Y-IFN was sufficient to induce maximal class I antigen expression by about 90% of cells after 3 days. At 50 units/ml Y-IFN, the cells showed maximal class II antigen expression for HLA-DR, whereas 100 units/ml I-IFN was required for maximal HLA-DQ expression. Higher concentrations of Y-IFN induced a further HLA-DP expression. However, serological HLA typing was performed after cell stimulation with 250 units/ml Y-IFN for 3 days. A concentration of 500 units/ml Y-IFN yielded equivalent results, but 750 units/ml Y-IFN led to poor identification of class I MHC specificities. Unclear serological results on class I specificities were clarified by 1D-isoelectric focusing (1D-IEF), thus allowing full HLA typing of all donor bulbi examined. In summary, successful HLA typing of cultivated RPE is dependent on both the Y-IFN concentration and the time lapse between stimulation and typing of the RPE. The method provides a much improved basis for cadaver cornea grafting.

Adolescent↗

[Incidence of retinal detachment after treatment with the Nd:YAG laser].

Two hundred fifty patients were examined after Nd:YAG laser capsulotomy and 330 patients retrospectively after Nd:YAG laser iridotomy. Retinal detachment followed in 3.6% of the capsulotomies. No correlation was found between the number of exposures or applied total energy and the risk for retinal detachment. The risk for retinal detachment, however, was found to be increased considerably by myopia and aphakia. After iridotomy, retinal detachment occurred in only one case, although similar energy levels were used for both procedures.

Follow-Up Studies↗

[Cefmenoxime penetration in human lacrimal sac mucosa after systemic administration].

Access to microbiological, pharmacokinetic and toxicological information is necessary for useful, controlled application of antibiotics in intraocular and periocular infections. It is important to know whether the antibiotic is effective against ophthalmologically relevant bacteria and if suprathreshold concentrations of the antibiotic can be achieved in the contaminated tissue. In the study presented we investigated the usefulness of cefmenoxime in cases of dacryocystitis. Lacrimal sac tissue--and serum specimens were obtained from 15 patients who underwent dacryocystorhinostomy 0.5 to 13 h after intravenous injection of 25 mg cefmenoxime kg. The usual Toti procedure was performed in 7 patients, whereas the other 8 underwent endonasal surgery. Out of the 15 patients 12 suffered from recurrent dacryocystitis. Before application of the antibiotic a serum control sample was obtained in all patients. The highest cefmenoxime levels in the lacrimal sac (72 mg/kg) were measured 30 min after injection. Thirteen hours after the injection, the cefmenoxime levels were too low to be measured. The levels of cefmenoxime in the lacrimal sac tissue were compared with the minimal inhibitory concentrations for the frequent occurrence of bacteria in lacrimal sac infections.

Adolescent↗

Ocular digitalis effects in normal subjects.

Several visual functions were examined before and during self-application of therapeutic doses of digitoxin. The ERG recordings showed a reduction of the critical flicker fusion frequency from 70 Hz to 35-40 Hz. Recovery of color vision after macular photostress was examined with Nagel's anomaloscope and Jaeger's tritanomaloscope. After digitoxin intake the matching range at the tritanomaloscope was enlarged. Following macular photostress the recovery time of both the Rayleigh and the Trendelenburg matches was significantly prolonged. The mesoptometer readings did not show any changes during the application of digitalis. This demonstrates that the process of neural adaptation is intact during digitoxin therapy. The error score in the Lanthony desaturated 15 panel test was slightly increased after digitalis application. The Farnsworth-Munsell 100-hue test showed a marked increase in the total error score. There were no changes in the standard panel D-15. The Ishihara pseudoisochromatic plates were read without mistakes after digitalis medication. The chromatic visual acuity for red-green and blue was examined by recording the maximum reading distance for the Velhagen pseudoisochromatic plates "65" (Jaeger's test) and "49". For both plates the reading distance was reduced by 50% during digitoxin therapy. Computerized perimetry by colored stimuli (Tübingen Automatic Perimeter by Aulhorn and Durst) did not reveal any definitive changes in sensitivity thresholds with therapeutic serum levels of digitalis. Spectral increment sensitivity for the isolated blue cone system (Wald-Marré approach) was not influenced by therapeutic doses of digitoxin. Topical digitoxin application (0.02 mg/10 ml) did not interfere with the pupillary light reflex (infrared pupillography) or with the accommodative amplitude or intraocular pressure. It did, however, result in toxic keratopathy with swelling of endothelial cells and edema of the corneal stroma and epithelium. All changes disappeared after withdrawal of digitalis.

Accommodation, Ocular↗