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Biomedical subjects

U Kellner

Publications and source records attributed to U Kellner.

At least 55 records · Page 3Linked to original sources
PubMed1998

Cone-rod dystrophy with serpentine-like retinal deposits.

OBJECTIVE: To describe the clinical and electrophysiologic findings in a novel retinal dystrophy. METHODS: Ophthalmologic and electrophysiologic examinations were performed in 3 affected members of 1 family: a 10-year-old girl, her 30-year-old mother, and her 59-year-old maternal grandfather. Electro-oculography (EOG) and electroretinography (ERG) were performed according to the standards of the International Society for Clinical Electrophysiology of Vision. RESULTS: In all 3 family members, gray, serpentine-like deposits were seen at the level of the retinal pigment epithelium (RPE). These were most distinct in the child, less prominent in her mother, and barely visible in the grandfather. Visual acuity was 20/25 OU in the child and 20/200 OU in both adults. Visual field testing showed normal outer limits and small paracentral scotomas in both adults. Electroretinographic recording revealed slightly reduced amplitudes in the 10-year-old girl, cone dysfunction in her mother, and cone-rod dysfunction in the grandfather. Multifocal ERG responses were reduced but recordable in the mother. The EOG light peak amplitude was normal in both females and borderline in the grandfather. The light peak was delayed in all 3 patients. CONCLUSIONS: Similar deposits at the level of the RPE have not been described in other inherited retinal dystrophies. This family appears to have a novel form of cone-rod dystrophy with deposits at the level of the RPE and probable autosomal dominant inheritance.

Adult↗
PubMed1998

[Hereditary macular dystrophies].

PURPOSE: Analysis of a consecutive series of patients suffering from hereditary macular dystrophies. PATIENTS AND METHODS: Between 1991 and 1997, 136 patients underwent clinical and electrophysiologic examinations (Ganzfeld ERG, EOG or multifocal ERG). RESULTS: The time of first examination was similar to the onset of clinical signs in most patients. In half of the patients onset was not before 40 years of age. In younger patients, Stargardt disease, X-linked retinoschisis and Best disease were the most frequent disorders. In patients aged 40 year and older, pattern dystrophies and central areolar choroidal dystrophy were more frequent. In 41 cases (30.2%) a specific diagnosis could not be made. Color vision and multifocal ERG were abnormal in all patients examined. Ganzfeld ERG was important for the diagnosis of X-linked retinoschisis, as was the EOG for Best disease. CONCLUSIONS: Hereditary macular dystrophies are a heterogeneous group of disorders. In several cases a definite diagnosis could not be made. Pattern dystrophies are the most frequent hereditary macular dystrophies in patients older than 40 years of age.

Adolescent↗
PubMed1998

Autosomal dominant vitreoretinochoroidopathy with normal electrooculogram in a German family.

BACKGROUND: Autosomal dominant vitreoretinochoroidopathy (ADVIRC) is a rare disorder previously described in four families residing in the USA and one family residing in Germany. We report the clinical and unexpected electrophysiological findings in a sixth family, residing in Germany. METHODS: An affected 23-year-old man, his 52-year-old affected mother and his 55-year-old unaffected father were examined by testing visual acuity, fluorescein angiography, visual fields, dark adaptation, electrooculography (EOG) and electroretinography (ERG). RESULTS: The 23-year-old man showed a circumferential retinochoroidal dystrophy extending from the mid-periphery to the ora serrata. There was a sharp demarcation between affected and nonaffected retina. Peripheral to the damarcation, bone spicules and yellow-white deposits were present, and the retinal vessels were severely attenuated. In addition, vitreous opacities were present. The EOG light rise was normal. The ERG amplitudes were reduced to 35% of the normal in all recording conditions. The 52-year-old mother showed marked peripheral pigmentation, but no bone spicules, deposits or vitreous opacities. Her EOG and ERG recordings were normal. CONCLUSIONS: Expression of ADVIRC can be very variable within the same family. A reduced EOG light rise, previously suggested as a characteristic sign for ADVIRC, is not a typical sign for all affected patients.

Adult↗
PubMed1998

Rubeosis iridis after vitrectomy for diabetic retinopathy.

BACKGROUND: Iris rubeosis and neovascular glaucoma (NVG) are serious complications of vitrectomy for proliferative diabetic retinopathy. The present study analyzes incidence and risk factors of these complications. METHODS: Preoperative and postoperative iris rubeosis were compared in 389 diabetic eyes after vitrectomy. Minimum follow-up was 6 months (median 26 months). Risk factors were studied using multivariate logistic regression analysis. RESULTS: Following vitrectomy, in 8.5% of the eyes stromal iris rubeosis developed de novo; NVG occurred in 5%. Significant risk factors for postoperative rubeosis were preexisting iris neovascularizations and postoperative retinal detachment. Six months after surgery, regression of preexisting iris rubeosis was observed in 57% of the eyes. In eyes without preoperative iris rubeosis, progression was found in 13% of cases 6 months postoperatively. CONCLUSION: With current surgical techniques iris rubeosis is more commonly regressive than progressive after vitreous surgery in diabetic eyes.

Adult↗
PubMed1998

Electrophysiological evaluation of visual loss in Müller cell sheen dystrophy.

AIMS: To describe the clinical picture and electrophysiological findings in Müller cell sheen dystrophy, a recently reported retinal dystrophy. METHOD: A basic ophthalmological evaluation as well as recording of standard electro-oculography and electroretinography were performed in one patient at the onset of visual loss and after 1 year of follow up. RESULTS: A 61 year old woman presented with visual loss in the right eye. Multiple folds at the level of the internal limiting membrane were seen at the posterior pole in both eyes. Macular oedema was present in the right eye. The visual acuity of the right eye was 6/30 and of the left 6/9. A paracentral scotoma was found in the right eye. Electro-oculographic examination of both eyes gave normal results. Electroretinography (ERG) revealed reduced b-wave and flicker amplitudes in the right eye; these potentials were normal for the left eye. The ON response in the right eye was reduced and delayed; it was normal in the left eye. A further loss of visual function was noted 1 year later in the right eye, but the ophthalmoscopic findings were unchanged. The ERG of the right eye had a negative waveform when dark adapted. Light adapted responses showed an unusual delayed b-wave, broad and delayed ON and OFF responses and a missing flicker response, suggesting a Müller cell dysfunction. Light adapted responses were slightly reduced in the left eye. CONCLUSIONS: Electrophysiological data indicate Müller cell dysfunction as a background of functional loss in Müller cell sheen dystrophy. This is in agreement with previously reported histological findings in this disorder.

Dark Adaptation↗
PubMed1998

Inner retinal function in hereditary retinal dystrophies.

Hereditary retinal dystrophies are most often disorders of photoreceptors and/or the retinal pigment epithelium. Structures secondary to the photoreceptor layer such as bipolar, horizontal, amacrine and ganglion cells are secondarily involved. In later stages of the disease a mild to moderate loss of inner retina occurs, but the second and third neurons remain surprisingly viable even in late and severe stages of retinal dystrophies. The function of the inner retina in patients suffering from hereditary retinal dystrophies is not easy to determine because it depends on the input of photoreceptors. The electroretinogram (ERG) offers several possibilities in this respect: b-wave, off-response (off-ERG), oscillatory potentials, scotopic threshold response of the flash ERG and the pattern ERG (PERG). We looked at two ERG tests: the PERG and the off-ERG. The PERG is an indicator of ganglion cell function. Its amplitude is related to the photoreceptor input determined by the flash ERG and visual field testing. But in cases of an undetectable flash ERG response the PERG can be recorded in some patients, but not in others. This may be an indication of a different effect on inner retinal function in different groups of patients. On- and off-responses are related to the function of depolarizing and hyperpolarizing bipolar cells. Evaluation of 301 patients with various retinal dystrophies revealed that most hereditary disorders primarily affect the photoreceptors or the pigment epithelium. In some patients, alterations of the on- and off-response amplitudes or implicit times were indicative of inner retinal disorders and different pathophysiologic mechanisms. However, interpretation has to be made carefully, as on- and off-responses may be influenced by dysfunction of photoreceptor synapses to bipolar cells, bipolar cells, Müller cells and intercellular matrix.

Adolescent↗
PubMed1998

[Vitrectomy in diabetic retinopathy: outcome, risk factors, complications].

BACKGROUND: Functional results, risk factors and complications of vitrectomy for diabetic retinopathy were studied to improve our estimation for benefits and risks of vitreous surgery with current techniques. MATERIALS AND METHODS: The course of 389 consecutive eyes, who had undergone vitreous surgery for complications of diabetic retinopathy within a four year period, was retrospectively reviewed. The minimum follow-up was 6 months, the median 26 months. Risk factors were studied using multivariate logistic regression analysis. RESULTS: Six months postoperatively 25% of the eyes had a visual acuity of 20/60 or better, a vision of less than 5/200 was found in 25% of the eyes. The most important risk factors were detachment of the macula and iris rubeosis. Only 16% of the eyes with tractional detachment of the macula had a postoperative vision of 20/200 or better, although in 86% the macula was anatomically successfully reattached. Postoperative retinal detachment was observed in 18% of all eyes. The incidence of this serious complication was only 5% after surgery for vitreous hemorrhage, but 54% after vitrectomy for tractional detachment of the macula. CONCLUSIONS: In eyes with advanced stages of long-standing tractional detachment of the macula, the functional prognosis is very poor due to the underlying microvascular disease. In less advanced stages with vitreous hemorrhage and flat retina the risk of vitreous surgery is low.

Adult↗
PubMed1997

Decreased drug accumulation in a mitoxantrone-resistant gastric carcinoma cell line in the absence of P-glycoprotein.

An established gastric-carcinoma cell line, EPG85-257P, is extremely sensitive to mitoxantrone (IC50, 0.12 ng/ml). Stepwise selection with mitoxantrone for 3 years resulted in a cell line (EPG85-257RN) that is 7,056-fold resistant to mitoxantrone (IC50, 846 ng/ml) and displays cross-resistance to the topoisomerase(topo)-II poisons ametantrone (411x), etoposide (112x) and teniposide (60x) as well as the topo-I poisons 7-ethyl-10-hydroxycamptothecin (331x) and topotecan (58x). We now show that this resistance is multifactorial. Western blotting revealed a 5-fold decrease in topo-IIalpha polypeptide in the mitoxantrone-resistant cells. Immunohistochemistry and Western blotting failed to demonstrate P-glycoprotein overexpression. Formation of trapped topo-II-DNA complexes in the resistant cells required higher mitoxantrone concentrations than in parental cells, even though nuclei isolated from the EPG85-257RN cells formed cleavage complexes normally. In agreement with these observations, which suggest the possibility of a defect in mitoxantrone accumulation, examination of mitoxantrone accumulation in both cell lines by confocal laser microscopy revealed that the EPG85-257RN cells accumulate less mitoxantrone at steady state. From these results, we propose that mitoxantrone accumulation, along with alterations in topo-IIalpha expression, contribute to the resistance to mitoxantrone observed in these cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

[Long-term vision follow-up after vitrectomy in diabetic retinopathy].

BACKGROUND: We investigated whether visual acuity remained stable in the long run after vitrectomy for complications of diabetic retinopathy and which risk factors for a decrease in vision could be identified. MATERIALS AND METHODS: The charts of 389 patients who had undergone vitreous surgery for complications of diabetic retinopathy between 1990 and 1994 were retrospectively reviewed. The median follow-up was 26 months with a minimum of 6 months. RESULTS: Seventy-two percent of the eyes with a vision of 20/200 or better within 6 months after surgery retained this vision after 2 years. The percentage of eyes with vision of less than 5/200 was 25% after 6 months and increased to 41% after 4 years. After 2 years 24% of the eyes had lost two or more lines compared to the best vision within the first 6 months after surgery. The main cause for a decrease of vision in type-I diabetics was retinal detachment, in type-II diabetics a progression of maculopathy and opticopathy. Risk factors for a detachment were pre-existing retinal detachment before surgery and reduced postoperative vision. The risk factor for a progression of maculopathy and opticopathy was a silicone tamponade. CONCLUSIONS: Eyes with good vision soon after surgery remain stable in the long run. Eyes with advanced stages of diabetic retinopathy and only ambulatory vision after surgery have an increased risk for new loss of visual function in the long run.

Adult↗
PubMed1997

[Electrophysiologic studies according to ISCEV (International Society for Clinical Electrophysiology of Vision) standards in children under 10 years of age].

PURPOSE: To analyze the value of electrophysiologic testing according to standards of the International Society for Clinical Electrophysiology of Vision (ISCEV) in infants less than 10 years of age. PATIENTS AND METHODS: In 64 infants less than 10 years, the results from of age electroretinograms (n = 47), visual evoked potentials (n = 30), or electro-oculograms (n = 1) were recorded. Twenty-nine infants were less than 6 years of age, and 17 infants were less than 3 years of age. Indications for examination were unexplained visual loss in 54 infants and familial hereditary retinal dystrophies in ten infants. Sedation with chloral hydrate was performed in seven children. RESULTS: In 40/64 infants (62%), the results of electrophysiologic examination were pathologic. In 29 infants visual loss was due to retinochoroidal dystrophies, and in 11 infants it was due to disturbances in the optic pathway. In 7/64, infants the suspected retinochoroidal dystrophy could be excluded. Therefore electrophysiologic testing was diagnostically accurate in 47/64 (73%) of cases. CONCLUSION: Electrophysiologic testing according to TSCEV standards can be reliably performed in infants less than 10 years of age. When the indication for electrophysiologic testing is made following meticulous ophthalmologic examination, diagnostic accuracy is given in at least 73% of cases.

Child↗
PubMed1997

Gyrate atrophy-like phenotype with normal plasma ornithine.

PURPOSE: To describe the clinical characteristics of a chorioretinal disease with a gyrate atrophy-like phenotype and normal plasma ornithine. METHODS: One family with three men who had progressive chorioretinal disease and three additional patients with simplex cases were examined clinically and with standard electroretinography, electrooculography, and dark adaptometry. RESULTS: In the family, a 70-year-old man and his two sons (39 and 41 years of age) were affected. On ophthalmoscopy, sharply demarcated peripheral patches of retinal pigment epithelium and choroidal atrophy were seen to progress to the posterior pole in the father's eye. In three unrelated men (62, 70, and 80 years of age), chorioretinal atrophy was present in the mid- and far periphery. Visual acuity was normal in the two youngest of all six patients; however, electroretinogram and electrooculogram waves were reduced. Advanced visual field defects and visual acuity loss occurred in the four older patients. Electroretinogram and electrooculogram were reduced, and the dark adaptation thresholds were elevated. In all patients, serum ornithine levels were normal. Ornithine-delta-aminotransferase activity in cultured skin fibroblasts and the apparent Michaelis constant (Km) for ornithine and alpha-ketoglutarate were within the normal range in all patients. CONCLUSIONS: A gyrate atrophy-like phenotype can result from causes other than deficient ornithine-delta-aminotransferase. Its occurrence in three male members in two generations in one family suggests an autosomal dominant inheritance in at least some such patients.

Adult↗
PubMed1997

RDS/peripherin gene mutations are frequent causes of central retinal dystrophies.

Patients from 76 independent families with various forms of mostly central retinal dystrophies were screened for mutations in the RDS/peripherin gene by means of SSCP analysis and direct DNA sequencing. Two nonsense mutations (Gln239ter, Tyr285ter), five missense mutations (Arg172Trp, Lys197Glu, Gly208Asp, Trp246Arg, Ser289Leu), and one single base insertion (Gly208insG), heterozygous in all cases, were detected. Only one of these mutations, Arg172Trp, has been reported previously. Cosegregation of the mutation with the disease phenotype could be established in selected families. Other missense mutations were excluded from a panel of 55-75 control subjects. The patients showed remarkable variation in phenotype and disease expression not only between cases with different mutations but also between affected members of the same family. This study indicates that RDS/peripherin mutations are a frequent cause of various types of central retinal dystrophies and that the RDS/peripherin gene exhibits a broad spectrum of allelic mutations. Comparative analysis of known mutations allowed us to hypothesise that the deleterious effect of RDS/peripherin gene mutations is the result of different molecular mechanisms.

Exons↗
PubMed1997

Detection of human topoisomerase II alpha in cell lines and tissues: characterization of five novel monoclonal antibodies.

We report five novel monoclonal antibodies (Ki-S1, Ki-S4, Ki-S6, Ki-S7, and Ki-S8) reactive with a proliferation-related nuclear antigen. In immunoprecipitation and Western blot experiments using crude nuclear extracts, they recognized a protein of 170 kD that, after proteolytic digestion of the immunoprecipitate and sequencing of the resulting peptides, was identified as the alpha-isoform of human topoisomerase II. This was confirmed by testing the antibodies on a highly purified enzyme preparation. Crossreactivity with topoisomerase II beta was ruled out by testing the antibodies on crude extracts from yeast cells expressing the beta-isoform exclusively. The antibodies bind the antigen with different affinities and at different epitopes, apparently located within the carboxyl third of the enzyme. All five antibodies are suitable for archival material after adequate antigen retrieval, thereby enabling retrospective studies. This report illustrates the tissue and subcellular distribution of the antigen through the cell cycle by immunohistochemistry and confocal fluorescence microscopy. The antibodies will be useful tools in further analysis of morphological and functional aspects of topoisomerase II and may serve diagnostic purposes, as well as providing prognostic information in tumor pathology.

Antibodies, Monoclonal↗
PubMed1997

Prognostic relevance of a novel proliferation marker, Ki-S11, for soft-tissue sarcoma. A multivariate study.

In 132 soft-tissue sarcomas and 52 benign soft-tissue tumors, cellular proliferation was examined by immunohistochemistry using monoclonal antibodies Ki-S11 (Ki-67 antigen) and Ki-S1 (topoisomerase II alpha) and by flow cytometric analysis of the S-phase fraction (SPF). Malignant tumors were graded histologically according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system. Patient age, sex, tumor location, histological type, and DNA ploidy were considered as additional prognostic variables. Consistent immunoreactivity was seen in approximately 95% of the cases, and determination of SPF was possible in approximately 60% Ki-S11 and Ki-S1 immunolabeling indices correlated in a linear manner. All proliferation parameters yielded significant differences between benign and malignant tumors. Ki-S11 and Ki-S1 immunoreactive scores also co-varied significantly with SPF, mitotic count, and histopathological grade. In univariate analysis, immunohistochemical proliferation indices, histopathological grade, mitotic count, and SPF were predictive of overall survival and the development of metastases. In multivariate analysis, immunolabeling scores of proliferation markers, grade, and SPF emerged as independent predictors of global survival and systemic progression. We conclude that the immunohistochemical assessment of proliferation, being more readily performable and more easily assessable than the equally relevant S phase fraction, may add appreciable information to the current prognostic models for soft-tissue sarcoma.

Adolescent↗