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Biomedical subjects

U Kellner

Publications and source records attributed to U Kellner.

At least 91 records · Page 5Linked to original sources

Anterior-chamber hypoxia and iris vasculopathy in pseudoexfoliation syndrome.

Iris vasculopathy is a well-recognized clinical feature in pseudoexfoliation syndrome (PES). In the present study we examined the morphology of the iris vasculature in PES using electron microscopy and we tested whether these iris vascular changes were correlated with an impaired oxygen supply to the anterior chamber. In the affected vessels we found a gradual degeneration of vascular cells, progressing from adventitial to endothelial cells, associated with the production of excess extracellular material, including pseudoexfoliative fibers. Oxygen partial pressure (pO2) was measured in the anterior chamber during cataract surgery using a polarographic oxygen electrode in eyes with and without PES. The pO2 value measured in the anterior chamber of 10 eyes without PES was 45 +/- 11 mmHg (mean +/- SD) in the chamber angle, 33 +/- 12 mmHg in front of the pupillary margin, and 13 +/- 8 mmHg in the center of the pupil. This spatial distribution of pO2 indicates that aqueous humor oxygenation occurs along the anterior iris surface. The mean pO2 values obtained in 8 patients with PES were 19 +/- 6 mmHg in the chamber angle, 16 +/- 4 mmHg in front of the pupillary margin, and 8 +/- 3 mmHg in the center of the pupil. We conclude that anterior-chamber hypoxia due to iris vasculopathy may represent a complication of PES that could play a role in the pathogenesis of PES-associated alterations in the anterior segment of the eye.

Aged↗

Radiation-induced optic neuropathy following brachytherapy of uveal melanomas.

In a prospective study the incidence of optic neuropathy following 106Ru/106Rh-brachytherapy of uveal melanomas was evaluated. Pattern visual evoked potentials (VECP) were measured before radiation and at regular follow-up intervals. Patients were grouped according to tumor location in peripheral melanomas with a central tumor margin of more than 60 degrees to the optic disc (n = 11) and central melanomas with a tumor within 15 degrees to the optic disc (n = 28). No patient with peripheral tumor had clinical signs of optic neuropathy or pathological VECPs after radiation. In patients with central melanomas clinical signs were seen in 5/28 (18%), but pathological VECPs developed in 14/28 (50%). The visual loss after radiation was greater in patients with pathological VECPs (P < 0.03). Radiation-induced optic nerve damage depends on tumor location and is more frequent than clinically expected.

Brachytherapy↗

Cone dystrophies with negative photopic electroretinogram.

A scotopic electroretinogram with an a-wave amplitude larger than the b-wave amplitude traditionally is termed 'negative'. Six male patients with negative photopic electroretinograms were examined; three of them suffered from progressive cone dystrophy, in which negative electroretinograms are unusual. Another patient without symptoms was the brother of a patient with cone dystrophy. These patients are compared with others who characteristically have negative electroretinograms-one patient with incomplete congenital stationary night blindness and another with X linked congenital retinoschisis. Differential diagnosis between these unusual cases of cone dystrophies and X linked retinoschisis or congenital stationary night blindness was possible with funduscopy, adaptometry, and evaluation of progression, but not with the electroretinogram. Inner retinal defects may occur in cone dystrophies as indicated by the negative electroretinogram. The waveform variations between our patients may be due to different inner retinal defects. The findings in two brothers indicate that cone dystrophy and inner retinal defects may be inherited separately.

Adolescent↗

[Androgen regulation of secreted growth factors in prostate carcinoma cell and tumor lines].

Previous studies have shown that part of steroid hormone action on hormone dependent carcinoma cells is mediated through secreted autocrine and paracrine growth factors. Coculture experiments using the androgen receptor positive human prostate carcinoma cell line LNCaP as feeder cells and the androgen receptor negative prostate cell line DU 145 as indicator cells, such as experiments with conditioned medium suggest that androgens might regulate proliferation of prostate carcinoma through a similar mechanism. LNCaP and DU 145 cells express high affinity EGF-receptors and show an increased growth rate under treatment with EGF, TGF alpha and FGF. The growth stimulating potential of LNCaP-conditioned medium can be enhanced by androgens. The polyanionic compounds suramin and dextran sulfates which have been shown to inactivate a variety of growth factors e.g. EGF/TGF alpha inhibit growth of LNCaP cells and DU 145 cells in a dose dependent and reversible fashion. Growth stimulation of LNCaP cells by EGF/TGF alpha can be completely reversed by simultaneous addition of polyanions but they inhibit androgen stimulation only partially. These data suggest the existence of at least two different mechanisms of growth regulation by androgens which can be distinguished by their different sensitivity of prostatic carcinoma cells to growth factor inhibitory agents. In order to investigate the therapeutic potential of these substances in complex, heterogeneous cell systems of solid tumors we treated 8 representative human prostate cancer lines in the nude mouse model. Systemic applications of polyanions revealed significant growth inhibition in hormone dependent as well as hormone independent xenografts. In androgen responsive lines growth inhibition was intensified by additional androgen withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

Oxygen in the anterior chamber of the human eye.

Oxygen partial pressure (pO2) was measured in the anterior chamber of the human eye during routine cataract surgery using a polarographic oxygen electrode. We found a reproducible spatial distribution of oxygen in the aqueous humor. The pO2 (n = 8) was 44.9 +/- 9.1 mmHg in the chamber angle, 35.0 +/- 10.9 mmHg above the pupillary margin, and 13.5 +/- 8.0 mmHg in front of the center of the pupil. Pretreatment of the eye with the alpha-adrenergic agonist phenylephrine (5%) resulted in a marked reduction in pO2 to 19.8 +/- 5.8 mmHg in the chamber angle, 13.4 +/- 4.7 mmHg above the pupillary margin, and 7.4 +/- 3.3 mmHg in front of the center of the pupil (n = 8). The pO2 in the anterior lens was very low (2.5 +/- 0.6 mmHg, n = 7). We conclude that oxygen is supplied at the anterior iris surface to the aqueous humor. The lens is an extremely low oxygen compartment. Topical phenylephrine causes anterior-segment hypoxia, probably by the constriction of iris vessels.

Aged↗

Pattern of dysfunction in progressive cone dystrophies--an extended classification.

An extended classification for progressive cone dystrophies is proposed on the basis of the retrospective analysis of the clinical and electrophysiological findings obtained in a series of 91 patients with progressive cone dystrophies and of a review of the literature. This classification depends on the different patterns of electroretinographic responses. Four main categories and ten subgroups are distinguished. Generalized cone dystrophies are most frequent (76/91), affect all types of cones, and may be subdivided according to the degree of rod involvement. In selective cone dystrophies (8/91), the three cone types are affected differently as detected with the color electroretinogram. They are subdivided on the basis of the cone type predominantly involved. Additional inner retinal transmission defects may occur in cone dystrophies (3/91). They are identified by an alteration in the b/a-wave ratio on the electroretinogram and may affect the cone or rod pathway. Localized cone dystrophies (4/91) are limited to certain retinal areas.

Adolescent↗

Hexadecylphosphocholine may produce reversible functional defects of the retinal pigment epithelium.

Hexadecylphosphocholine is a synthetic phospholipid derivative that has antitumor activity due to its interference with membrane functions. Animal experiments have shown photoreceptor and retinal pigment epithelium (RPE) degeneration after its systemic application. In a phase II trial of hexadecylphosphocholine therapy in 23 patients with advanced metastatic colorectal or lung cancer, visual acuity and color vision testing, slit-lamp examination, tonometry, fundoscopy (including photodocumentation), visual field testing, electrooculography (EOG), and electroretinography (ERG) were performed. A baseline examination was carried out prior to therapy. Patients were reexamined after 2 months and after 5 months. In all, 71% of the patients had a reduced light peak in the EOG during therapy. After the end of therapy the light peak improved again and became normal in most patients. The statistical analysis showed that the light-peak values during therapy were significantly lower than the baseline and posttreatment values. This indicates that hexadecylphosphocholine might be capable of producing a partly reversible functional defect of the RPE. Apart from this finding, no other functional or morphological ocular side effect was detected. The functional changes observed in our patients as well as the morphological changes found in animal experiments are similar to those reported for known diseases of the RPE-photoreceptor complex. Therefore, hexadecylphosphocholine-induced retinopathy might become useful as an animal model for such diseases.

Adenocarcinoma↗

Variation of temporal stimulus characteristics to evaluate visual function prior to pars plana vitrectomy.

Electrophysiological examinations were carried out prior to pars plana vitrectomy in a series of consecutive patients with complicated diabetic retinopathy, proliferative vitreoretinopathy, and perforating injuries. In 141 eyes electroretinograms were evaluated. The amplitude of the a- and b-waves at dark and light adaptation and of the 30-Hz flicker response correlated with the postoperative visual acuity and the retinal morphology. Due to the variability of these parameters, however, the preoperative electroretinogram has no predictive value. In 245 eyes, flash and flicker (5, 10, 20, 30 Hz) visual evoked cortical potentials (VECP) were recorded. The flash VECP was of no value. The presence of a response to a flicker stimulus of 10 Hz or higher frequencies, however, indicated a better functional recovery (P < 0.02). More eyes with an attached central retina showed a 30-Hz flicker response as compared to eyes with central retinal detachment (P < 0.01). The flicker VECP therefore, has a predictive value prior to vitrectomy.

Dark Adaptation↗

Color electroretinography. A method for separation of dysfunctions of cones.

Electroretinograms to white and color stimuli were recorded in four normal subjects and nine subjects with different cone dysfunctions, including protanopia, cone dystrophy, cone dystrophy with supernormal b-waves at dark adaptation, cone dystrophy with missing b-waves during light adaptation and rod-cone dystrophy with blue cone hypersensitivity. Color stimuli were obtained with Kodak Wratten filters in blue, blue-green, green, yellow and red. Electroretinograms to all stimuli were recorded during dark and light adaptation with different stimulus intensities and to 30-Hz flicker stimulation. In protanopia, responses to red during light adaptation and flicker stimulation were reduced. All cone dystrophies showed reduced amplitudes and prolonged implicit times to red when dark adapted. The light-adapted responses were equally reduced to all color stimuli in cone dystrophy and cone dystrophy with supernormal b-waves. Contrary to other cone dystrophies, in cone dystrophy with missing b-waves, responses to red were severely reduced and responses to green were preserved, indicating a predominantly red cone dysfunction. Blue cone hypersensitivity was clearly distinct from other dystrophies in having large response to blue and blue-green and much smaller responses to all other colors in all stimulus conditions. The electroretinogram with color stimuli allowed separation of different cone dysfunctions and identification of new retinal dysfunction syndromes.

Adaptation, Ocular↗

[Colored light stimuli in ERG for differential diagnosis of cone dystrophies].

We recorded electroretinograms (ERG) with white and color stimuli in normal persons and four patients with cone dystrophies. Kodak Wratten-filters in blue, blue-green, green, yellow and red were used for the color flashes. ERGs to all color stimuli were recorded at dark and light adapted conditions with different stimulus intensities, to 30 Hz flicker stimulation and with special filtering for oscillatory potentials. Selective blue cone-responses were obtained using strong blue flashes at a yellow background. Patients with cone dystrophies showed slightly to moderately reduced responses at dark adaptation to blue, blue-green, green and yellow stimuli. Red stimuli elicited only small responses with a markedly delayed b-wave implicit time. The light adapted recordings, flicker responses and oscillatory potentials were reduced to all color stimuli. However, differences between patients with cone dystrophies could be detected concerning the responses to red and green. In two patients the responses were reduced to the same degree to all color stimuli. Another patient had very small responses and no oscillatory potentials to red, but his responses were only moderately reduced to green. A patient with combined red-green cone and rod dystrophy had a blue cone hypersensitivity. Responses to blue and blue-green were large at all stimulus conditions, but responses to all other stimuli were much smaller. The blue cone ERG showed a prominent blue cone response. ERG recording to colored stimuli allows a separation of retinal dysfunction in patients with cone dystrophies.

Adult↗

Cone dystrophies: clinical and electrophysiological findings.

We analyzed the clinical and electrophysiological findings of 77 patients suffering from progressive cone or cone-rod dystrophies. The onset of symptoms was at the average age of 19.7 +/- 19.4 years. In some patients, the disease started within the 5th decade. The mean visual acuity was 0.19 +/- 0.2, while in 38%, the visual acuity was lower than 0.1. Color vision defects and visual field defects were found in most patients. The electrooculogram was recorded in 59 patients and was normal in only 19. On the electroretinogram (ERG), 60 patients had a reduction of the 30-Hz flicker amplitude and of the responses at maximum stimulus intensity when dark and light adapted. The ERG alterations showed a correlation to the visual field defects and to the reduction of the light rise on the electrooculogram. No correlation existed between the ERG amplitudes and visual acuity or color vision. Ophthalmoscopically, the posterior pole was normal in 25 patients. In the remaining patients, fundus changes ranged from mild pigment irregularities to severe pigment clumping. No correlation between fundus changes and functional findings existed.

Adolescent↗

Growth factors in human prostate cancer cells: implications for an improved treatment of prostate cancer.

It has been previously shown that estrogens may exert their action on human breast cancer cells through coordinated control of secreted growth factors which act in an autocrine and paracrine fashion. Growth stimulation of the androgen receptor negative prostate carcinoma cell line DU-145 by dihydrotestosterone in the presence of the androgen-responsive human prostate carcinoma cell line LNCaP now indicates that androgens may regulate growth of prostate carcinoma cells through related mechanisms. A variety of androgen-regulated growth modulatory activities with autocrine and paracrine potential can be detected in conditioned media from LNCaP cells partially purified by ion exchange chromatography. Androgen-induced growth of LNCaP cells is partially inhibited by the polyanions suramin and dextran sulfates which antagonize growth factor action. These data suggest the existence of at least two different mechanisms of growth regulation by androgen which can be distinguished by their different sensitivity to growth factor inhibitory agents. We conclude that the combination of antipeptidergic substances and androgen withdrawal would represent a new and promising strategy for treatment of human prostate cancer.

Cell Division↗

[Retinal degeneration with blue cone hypersensitivity].

The clinical and electrophysiological findings are presented for five patients who had enhanced blue cone sensitivity. This new syndrome is characterized by night blindness, yellow, partly pigmented flecks at the posterior pole and variable visual loss. Maculopathy and peripheral retinoschisis may occur. The electroretinogram shows similar responses to dark and light-adapted conditions and long b-wave implicit times. This was the first time that it could successfully be demonstrated that the disease is really inherited and is probably of autosomal recessive origin. The main diagnostic test is an ERG recording with blue and red stimuli in the light-adapted state. These patients show enhanced sensitivity for blue instead of red when compared to normals and other retinal degenerations.

Adolescent↗

[Revision operations in retinal redetachment].

We analyzed retrospectively 239 consecutive patients who had undergone reoperation for repeat retinal detachment; 441 repeat operations were performed. The average follow-up was 2.1 years, and on average we noted 1.8 retinal redetachments per patient. At the last follow-up examination in 173 eyes (72.4%), the retina was reattached; 10.5% of the eyes had a partially detached retina and in 15.9% the retina was again completely detached. Enucleation was necessary in 3 eyes (1.2%). Visual improvement occurred in 45% of the eyes with reattachment of the retina. When the first retinal detachment occurred, 74 eyes were aphakic. Compared to the other 165 eyes there was no difference in anatomic or visual outcome. Aphakic eyes needed fewer additional reoperations (39%) compared to the phakic group (50%, p less than 0.01). One important reason for the surgery being unsuccessful was poor placement of the scleral buckle. In both groups equatorial placement of the scleral buckle led to anatomical success in more than 50%. The eyes in the aphakic group required more vitrectomies (47%) compared to the phakic eyes (34%, p less than 0.01).

Adolescent↗

Diagnostic clinical findings of a new syndrome with night blindness, maculopathy, and enhanced S cone sensitivity.

We studied eight patients who had night blindness, maculopathy (often cystoid), degenerative changes in the region of the vascular arcades, relatively mild visual field loss, and an unusual but characteristic electroretinogram. The dark-adapted electroretinogram showed no response to low-intensity stimuli that normally activate the rods, but large, slow responses to high-intensity stimuli. These large, slow waveforms persisted without change under light adaptation, and showed a striking mismatch to photopically balanced short and long wavelength stimuli (with sensitivity much greater to short than long wave-lengths). Since there is evidence from other studies that the electroretinogram and psychophysical responses represent hypersensitivity of short wavelength-sensitive (S or blue) cones, we propose that this disorder be called the enhanced S cone syndrome. There can be different degrees of severity in this syndrome, and progression appears to be slow.

Adolescent↗

X-linked congenital retinoschisis.

The natural history and electrophysiological findings of 52 patients with X-linked congenital retinoschisis with a follow-up of up to 26 years are described. The mean visual acuity was reduced to 0.24 +/- 0.2 and remained unchanged in most patients during this time. If visual loss occurred, it usually happened in the first decennium. The complications were retinal detachments in 11% and vitreous hemorrhages in 4% of the eyes. In general, the vitreous hemorrhages resolved spontaneously. Retinal detachments were treated successfully with conventional buckling procedures. Redetachments occurred in about 40%. Prophylactic laser coagulation was of no use because it was complicated by detachment in 43% of our series. The electro-oculogram was usually normal. In addition to the known electrorentinographic findings of normal a-wave and reduced b-wave amplitudes, we found prolonged b-wave latencies and implicit times, as well as a reduced 30 Hz flicker response.

Adolescent↗

Cone dystrophy and supernormal dark-adapted b-waves in the electroretinogram.

A male patient suffering from cone dystrophy was followed over 9 years. In addition to the typical clinical and electrophysiologic signs, supernormal b-waves were found in the dark-adapted electroretinogram. Our case is compared with 12 similar patients described in the literature. Our patient differed from the other patients in the following aspects: he was male and had a congenital stationary disease with a small pigment epithelial scar in the left eye only and no other fundus changes up to the age of 22 years. He did not complain of night blindness. The dark-adapted electroretinogram of our patient showed a normal b-wave threshold with increased b-wave amplitudes and markedly prolonged b-wave latencies and implicit times. This combination of signs has not been reported to date in any other patient and points towards a postreceptoral defect of the interneuronal connection.

Adolescent↗