Universitäts-Frauenklinik des Saarlandes

The human endogenous retrovirus K10 (HERV-K10) has been identified in the human genome by its homology to retroviruses of other vertebrates (M. Ono, T. Yasunaga, T. Miyata, and H. Ushikubo, J. Virol. 60:589-598, 1986). Using PCR amplification, DNA cloning, sequencing, and procaryotic expression, we were able to demonstrate that HERV-K10 encodes a 73-kDa protein which was processed by a HERV-K10-encoded protease to yield proteins p22/p26, p30, and p15/16. Analysis of the teratocarcinoma cell line Tera 1 or tumor tissues by immunoblotting demonstrated that the 80-kDa polyprotein of HERV-K10 gag and a processed protein of 39 kDa were expressed. In addition, a major protein of 39 kDa and additional species of 30, 22, 19, and 17 kDa could be detected in the supernatant of Tera 1 cells, suggesting that HERV-K10 Gag proteins are either secreted or processed to probably incomplete viral particles. In addition, the gag gene of HERV-K10 was expressed in the baculovirus system. Using this recombinant system to test antisera from patients with different diseases and healthy individuals, we were able to detect antibodies against the N-terminal part of HERV-K10 Gag in 2 to 4% of groups of tumor patients with titers ranging between 1:80 and 1:640, while approximately 0.1 to 0.5% of healthy individuals exhibited antibodies with lower titers. In contrast, patients with seminoma had antibody titers in the range of 1:2,560 at the time when the tumor was detected. Immunohistochemistry using specific rabbit sera or monoclonal antibodies against HERV-K10 Gag revealed that the Gag protein is expressed in the cytoplasm of the tumor cells. Furthermore, an 80-kDa protein corresponding to the HERV-K10 Gag polyprotein could be detected in tumor biopsies. For the first time, these data indicate that HERV-K10 Gag proteins are synthesized in seminoma cells and tumors exhibit relatively high antibody titers against Gag. So far, no information on which role HERV-K10 plays in the development of this tumor exists.

PURPOSE: Hitachi real-time tissue elastography (HI-RTE) is an ultrasound technique that facilitates the estimation of tissue elasticity. Our study evaluates whether sonoelastography improves the differentiation of benign and malignant breast lesions. MATERIALS AND METHODS: In a multicenter approach sonoelastography of focal breast lesions was carried out in 779 patients with subsequent histological confirmation. We present data from 3 study centers (Berlin, Bielefeld, Homburg/Saar) focusing on the sensitivity (SE), specificity (SP) and the positive (PPV) and negative predictive value (NPV) of sonoelastography. In addition we performed an analysis of the diagnostic performance, expressed by the pretest and posttest probability of disease (POD), in BI-RADS®-US 3 or 4 lesions as these categories can imply both malignant and benign lesions and a more precise prediction would be a preferable aim. RESULTS: Sonoelastography demonstrated an improved SP (89.5 %) and an excellent PPV (86.8 %) compared to B-mode ultrasound (76.1 % and 77.2 %). Especially in dense breasts ACR III-IV, the SP was even higher (92.8 %). In BI-RADS-US 3 lesions, a suspicious elastogram significantly modified the POD from 8.3 % to a posttest POD of 45.5 %. In BI-RADS-US 4 lesions, we found a pretest POD of 56.6 %. The posttest POD changed significantly to 24.2 % with a normal elastogram and to 81.5 % with a suspicious elastogram. CONCLUSION: Our data demonstrates that the complementary use of sonoelastography definitely improves the performance in breast diagnostics. Finally we present a protocol of how sonoelastography can be integrated into our daily practice.

Oculocutaneous albinism (OCA) is caused by a deficiency of melanin synthesis and characterized by generalized hypopigmentation of skin, hair, and eyes. Due to the hypopigmentation of the retinal pigment epithelium, OCA is usually associated with congenital visual impairment, in addition to an increased risk of skin cancer. OCA is a genetically heterogeneous disease with distinct types resulting from mutations in different genes involved in the pathway which results in pigmentation. OCA1 is associated with mutations in the TYR gene encoding tyrosinase. OCA2 results from mutations in the P gene encoding the P protein and is the most common form of OCA. OCA3, also known as rufous/red albinism, is caused by mutations in the TYRP1 gene, which encodes the tyrosinase-related protein 1. Recently, OCA4 was described as a new form of OCA in a single patient with a splice site mutation in the MATP gene (or AIM1), the human ortholog of the murine underwhite gene. The similarity of MATP to transporter proteins suggests its involvement in transport functions, although its actual substrate is still unclear. We screened 176 German patients with albinism for mutations within the MATP gene and identified five individuals with OCA4. In this first report on West European patients, we describe 10 so far unpublished mutations, as well as two intronic variations, in addition to two known polymorphisms.

We report 11 patients seen between 1991 and 1994 with oral lichenoid lesions (OLL). In 10 cases, there was contact with dental amalgam fillings, and in patient no. 10 with both amalgam restorations and a gold crown. The last patient had, in addition to her OLL, lichen planus of the skin and genital mucosa. In 5 cases, combined sensitization to mercury and other metal salts, particularly gold sodium thiosulfate (GST) and palladium chloride (PDC), was observed. In 10 patients, the lesions considerably improved or totally cleared within 1 to 9 months of replacement of restoration materials. Histological examination of biopsies from the test sites of amalgam, mercuric chloride, GST and PDC, taken 10 or 17 days after application of patch tests, showed lichenoid changes in 7 patients with at least 1 of the allergens. As at least 2 patients had inflammatory lesions of the oral mucosa related to both amalgam and gold restorations, combined sensitization to inorganic and organic mercury derivatives, GST and, in 1 case, PDC, a "dental restoration metal intolerance syndrome" is proposed.

Atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lpa) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL adsorption and LDL hemoperfusion. Regarding the different LDL apheresis systems used, there is no significant difference with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein (HDL), or triglyceride concentrations. With respect to elevated Lpa levels, however, the immunoadsorption method seems to be the most effective. In 45 patients (25 women, 20 men) suffering from familial hypercholesterolemia resistant to diet and lipid lowering drugs, low-density lipoprotein (LDL) apheresis was performed over 95.6 +/- 44.7 months. Four different systems (Liposorber, 32 of 45, Kaneka, Osaka, Japan; Therasorb, 6 of 45, Baxter, Munich, Germany; Lipopak, 2 of 45, Pocard, Moscow, Russia; and Dali, 5 of 45, Fresenius, St. Wendel, Germany) were used. With all methods, average reductions of 57% for total cholesterol, 55.9% for LDL, 75.8% for lipoprotein a (Lpa), and 45.9% for triglycerides, and an average increase of 14.3% for HDL were reached. Severe side-effects such as shock or allergic reactions were very rare (0.3%) in all methods. In the course of treatment, an improvement in general well-being and increased performance were experienced by 44 of 45 patients. The present data demonstrate that treatment with LDL apheresis of patients suffering from familial hypercholesterolemia resistant to maximum conservative therapy is very effective and safe even in long-term application.

AIMS: The Medtronic Engager™ aortic valve bioprosthesis is a self-expanding valve with support arms facilitating anatomically correct positioning and axial fixation. Valve leaflets, made of bovine pericardium, are mounted on a Nitinol frame. Here, we report the first in man study with this new implant (Trial Identifier NCT00677638). METHODS AND RESULTS: Thirty patients (mean age 83.4 ± 3.8 years; 83% female) with tricuspid aortic valve stenosis were included in the study. Mean logistic EuroSCORE was 23.4 ± 11.9. Mean aortic annulus diameter was 21.8 ± 1.4 mm. For this study, the Engager was available in only one size (23 mm), to fit aortic annuli of 19-23 mm. Standard transapical valve implantation was performed using pre-dilation of the aortic valve and rapid ventricular pacing during balloon valvuloplasty and most valve deployments. Accurate valve placement was achieved in 29/30 cases (97%). Post-implant peak-to-peak gradient was 13.3 ± 9.3 mmHg. In 80% of the patients, no more than grade I paravalvular leakage was observed, in 13% grades I-II and in 3% grade II. Three patients (10%) required permanent pacemaker implantation for higher-degree or complete atrioventricular block. Four dissections (13%) occurred during positioning of the valve and were treated surgically in three cases. Thirty-day and in-hospital mortality were 20% and 23%, respectively, and 6-month survival was 56.7%. No structural failure occurred for up to 1 year. CONCLUSION: This series established the feasibility of implanting a novel self-expanding transapical aortic valve prosthesis predictably into an anatomically correct position. Observed complications led to complete redesign of the delivery system for upcoming clinical studies with the goal of establishing safety and performance.

Avulsion fractures of the lateral tibial plateau, known as the lateral capsular sign, are increasingly associated with anterior cruciate ligament (ACL) ruptures. This phenomenon, known as the Ségond fracture, is a bony avulsion of the meniscotibial ligament. Stress, which can lead to an avulsion of this kind, almost always occurs during knee flexion and internal tibial rotation, and in most cases only after damage to the primary ACL stabilizer. Examination of 151 ACL ruptures revealed a Ségond fracture in 9% of patients. Nearly all were caused by sports injuries and, understandably, the accident mechanism always included knee flexion and internal rotation of the tibia. In a similarly large number of other knee injuries without damage to the ACL, only one case of a Ségond fracture was found. This phenomenon, which is easy to detect by radiograph, can thus be regarded as a strong indication of the presence of a ligament injury.

Low-density lipoprotein (LDL) apheresis is an extracorporeal modality to lower LDL cholesterol. While most of the devices eliminate LDL particles from plasma, a recently introduced whole-blood perfusion column (DALI) adsorbs lipoproteins directly from whole blood. We investigated the efficacy and safety of a new whole-blood LDL apheresis system (Liposorber D) in 10 patients with severe hypercholesterolemia in a multicenter trial. In 93 LDL aphereses, the mean reduction in LDL cholesterol and lipoprotein(a) was 62.2 +/- 11.5% and 55.6 +/- 16.9%, respectively (P < 0.01). If hemodilution during apheresis was considered, the reductions were 58.0 +/- 10.9 and 55.3 +/- 10.9%, respectively (P < 0.01), while high-density lipoprotein (HDL) cholesterol did not change significantly. Three mild episodes of hypocalcemia and two mild episodes of arterial hypotension were observed; however, LDL apheresis could be continued in each case. In conclusion, the new whole-blood LDL apheresis with Liposorber D is a safe, simple, and useful modality to reduce LDL cholesterol and lipoprotein(a) in cardiovascular high-risk patients.

INTRODUCTION: The Retro-IDEAL (ILUVIEN Implant for chronic DiabEtic MAcuLar edema) study is a retrospective study designed to assess real-world outcomes achieved with the ILUVIEN® (0.19 mg fluocinolone acetonide (FAc)) in patients with chronic diabetic macular edema (DME) in clinical practices in Germany. METHODS: This study was conducted across 16 sites in Germany and involved 81 eyes (63 patients) with persistent or recurrent DME and a prior suboptimal response to a first-line intravitreal therapy (primarily anti-VEGF intravitreal therapies). RESULTS: Patients were followed-up for 30.8 ± 11.3 months (mean ± standard deviation) and had a mean age of 68.0 ± 10.4 years. Best-recorded visual acuity (BRVA) improved by +5.5 letters at month 9 (P ⩽ 0.005, n=56; from a baseline of 49 letters) and this was maintained through to month 30 (P ⩽ 0.05, n = 42). There was a concurrent improvement in central macular thickness with a reduction from 502 µm at baseline to 338 µm at year 1 (P ⩽ 0.0001, n = 43). This effect was sustained to year 3 (i.e. 318 µm; P ⩽ 0.0001, n = 29). Mean intraocular pressure (IOP) remained constant between baseline and year 3 with a peak change of 1.9 mm Hg occurring at year 1. Elevated IOP was observed in a similar percentage of patients prior to (22.2% of cases) and following (27.2%) treatment with the FAc implant. In the majority of cases, these elevations were managed effectively with IOP medications. CONCLUSIONS: Despite substantial amounts of prior intravitreal treatments - primarily with anti-vascular endothelial growth factor (VEGF) drugs - this real-world study showed that sustained structural and functional improvements can last for up to 3 years with a single FAc implant.

We report a patient with contact stomatitis due to combined sensitization to palladium and platinum. Patch testing showed strong and persistent allergic patch test reactions to palladium chloride (1% pet.), ammonium tetrachloroplatinate (0.25% pet.), and a palladium metal plate. A platinum metal plate showed a weaker reaction. Histological examination of a biopsy from the test site of palladium chloride (1% pet.) at D3 showed both eczematous and lichenoid changes.

First-rank symptoms of schizophrenia, such as thought insertion, thought broadcasting, "made" volition, and delusional perception, were introduced for purposes of diagnosis into a German university clinic. Such "Schneiderian" criteria were evaluated in 210 case records. Ratings employed formal definitions. Of 210 records examined, 69 (33%) of the schizophrenic patients had first-rank symptoms. The frequency of finding such symptoms in a group of schizophrenics is compared to other reports. There are considerable differences in frequency of individual symptoms as well as total number of such symptoms across centers, but the use of precisely agreed on definitions of first-rank symptoms may lead to better agreement.

4 patients developed an erythema-multiforme-like reaction following acute contact dermatitis from 2 different bufexamac-containing topical preparations. Histologically, the lesions did not show changes that were typical of erythema multiforme. Patch testing gave positive reactions to bufexamac at 1, 2, 3 and 4 days. The histological picture of 2 positive test reactions was suggestive of a drug reaction in the 1st, and of an acute eczematous reaction in the 2nd, case. A systemic allergic reaction with spread of lesions could have been involved, following percutaneous absorption of the allergen.

Eye muscles and the sphincter muscles of the bowel and bladder were formerly thought to be spared in amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder. As frequent subclinical impairment of the anal sphincter muscles in ALS has recently been reported, We suspected an earlier and more frequent, if subclinical, involvement of the oculomotor system than hitherto described. Starting in 1993, we repeatedly studied oculomotor involvement in eight patients with (ALS) using routine orthoptic examination techniques as well as electro-oculographic recordings of ocular movements. Three patients had consistently normal clinical examinations but progressive changes in electro-oculography (EOG). Three patients showed intermittent impairment of eye movements with normal EOG (one patient) or with progressive changes on EOG examination. In two patients, both clinical examination and EOG were progressively pathologic. These findings provide further evidence of early oculomotor involvement, e.g., prior to respiratory failure, in ALS than previously suspected. Since EOG changes seemed to be detectable in all but one patient, EOG changes may allow earlier, subclinical detection of impaired eye movement and thus reveal even an increased frequency of oculomotor impairment in ALS. Due to the heterogeneity of ALS the number of patients examined to settle finally the question of oculomotor involvement in ALS needs to be increased. Newly developed software will allow further interpretation and comparison of more data and, thus, should offer further help in detecting early changes.

OBJECTIVE: To investigate ovulation inhibition with drospirenone, a novel progestogen that has a profile similar to natural progesterone, when given alone or in combination with ethinylestradiol. METHOD: Hormonal parameters (LH, FSH, 17beta-estradiol and progesterone) and peripheral parameters (cervical score, spinnbarkeit and crystallization), as well as follicle size assessed by ultrasonography, were measured in two groups of healthy women. Forty-eight women aged 19-35 years were randomly assigned to receive 0.5 mg, 1.0 mg, 2.0 mg or 3.0 mg of drospirenone over a single treatment cycle, and 52 women aged 20-35 years were randomized to receive either 2 mg drospirenone/30 microg ethinylestradiol or 3 mg drospirenone/30 microg ethinylestradiol over three treatment cycles. Baseline measurements were taken during a control pretreatment cycle. RESULTS: Adequate ovarian suppression with drospirenone alone was evident at dose levels of 2 and 3 mg, and at 3 mg all subjects had anovulatory cycles. Although both combined preparations (2 mg and 3 mg drospirenone/30 microg ethinylestradiol) inhibited the hypothalamic-pituitary-ovarian axis, follicular maturation leading to escape ovulation was observed in three subjects in the 2 mg drospirenone/30 microg ethinylestradiol group. Only one of these ovulations was considered to be definitely the result of treatment failure. All cycles in the 3 mg drospirenone/30 microg ethinylestradiol group were anovulatory. No statistically significant difference was found between treatment groups. CONCLUSION: The combination of 3 mg drospirenone/30 microg ethinylestradiol (Yasmin, Schering AG) reliably inhibits ovulation, with a low frequency of follicular maturation, and provides a reasonable safety margin.

Oculocutaneous albinism (OCA) in man may be caused by mutations within the tyrosinase gene (TYR) resulting in OCA1. Analysing patients with recessively inherited albinism we found DNA variations in 82 unrelated individuals. 53 out of 78 mutations and polymorphisms revealed by this study are not published previously. The changes include 68 nucleotide substitutions resulting in amino acid changes, stop mutations and polymorphisms as well as four nucleotide insertions and six deletions. Furthermore, we found an accumulation of three to five mutations in 17 patients with OCA1. © 2004 Wiley-Liss, Inc.

Die inhalative Applikation von Medikamenten ist die bedeutsamste Form der Behandlung von obstruktiven Atemwegserkrankungen [30] [75] [99]. Gründe hierfür sind die hohe lokale Wirkstoffkonzentration bei geringer Gesamtdosis und das damit verbundene günstige Wirkungs-/Nebenwirkungsverhältnis (z. B. Glukokortikoide) sowie der rasche Wirkungseintritt (z. B. Beta-2-Adrenergika) [2] [73] [113] [114]. Neben Medikamenten zur topischen Therapie wird zunehmend die Inhalation verschiedener Substanzen zur systemischen Behandlung geprüft [17] [19] [59] [60] [65] [93]. Darüber hinaus werden neue Applikationssysteme entwickelt [93]. Die große Auswahl von Inhalationssystemen führt nicht selten zu einer Unsicherheit bei Ärzten und Patienten, obgleich sie die Möglichkeit bietet, für jeden individuellen Fall ein geeignetes System auszuwählen. Hierfür ist die Kenntnis einiger Grundsätze der Aerosolmedizin und technologischer Aspekte der Inhalationsbehandlung erforderlich.

Numerous in vitro and in vivo observations, demonstrating that 1,25-dihydroxyvitamin D(3) is a potent inhibitor of tumor cell growth, provided the rationale for using this seco-steroid hormone to treat patients with leukemia and various types of cancer. However, the therapeutic efficacy of systemically applied vitamin D analogs for treating cancer has not yet fulfilled its promise. A main reason for these disappointing results is that the use of systemically applied vitamin D analogs is limited by severe side effects, mostly hypercalcemia, at the supraphysiological doses needed to reach clinical improvement. New concepts for the development of cancer treatment strategies that are based on the use of vitamin D(3) compounds are discussed in this manuscript. At the moment, different strategies that may enable the application of vitamin D analogs for the treatment of various malignancies, including malignant skin tumors, are employed. It has been shown that certain vitamin D analogs differ in their intracellular metabolism, nongenomic actions, pharmacokinetics, interaction with the vitamin D binding protein (DBP) or the vitamin D receptor (VDR). Several of these new concepts are based on recent laboratory results demonstrating that VDR requires heterodimerisation with additional nuclear cofactors such as the retinoid-X receptor (RXR) for sufficient DNA-binding or are based on new findings in the metabolism of vitamin D. Taken together, these new strategies hold promise that analogs of 1,25-dihydroxyvitamin D(3) may herald a new era in the treatment of various malignancies, including skin cancer.

We aimed to evaluate potential correlation between ovarian activity during use of combined oral contraceptives and the incidence of intermenstrual bleeding. Data from seven prospective clinical studies with five different combined low-dose oral contraceptives were retrospectively analyzed to determine ovarian activity measured by the Hoogland Score (follicle diameter and endogenous hormone levels) and cycle control. A total of 227 young fertile women were evaluated over three treatment cycles each. Women with intermenstrual bleeding had statistically significantly higher estradiol levels than those without intermenstrual bleeding. Also, women with intermenstrual bleeding had significantly larger follicle-like structures than those without intermenstrual bleeding. For example, in the second treatment cycle the difference of the mean follicle diameters between women without intermenstrual bleeding (12.5 mm) and women with spotting (16.9 mm) or breakthrough bleeding (16.1 mm) was statistically significant (p = 0.0179). Less than 17% of women with Hoogland Score 1, 2 or 3 (low ovarian activity) reported intermenstrual bleeding. On the other hand, 35.2% of women with Hoogland Score 4 (active follicle-like structures) reported intermenstrual bleeding. The association between bleeding and Hoogland Score was statistically significant (p < 0.0011). The findings of this retrospective analysis provide evidence that high ovarian suppression is positively correlated with improved cycle control in terms of less frequent intermenstrual bleeding - slight and heavy.

We report a patient with occupational contact dermatitis due to sensitization to mancozeb and perhaps metiram used in a vineyard. Patch testing showed strong allergic patch test reactions to 2 of the commercially available preparations used (Dithane Ultra and Polyram WG). Further patch tests showed allergic patch test reactions to mancozeb (0.5 and 1% pet.), a weak reaction to metiram (1% pet.) as well as to 4 other fungicides of the dithiocarbamate group (maneb, nabam, propineb and zineb), which had never been used in the vineyard.

In der vorliegenden klinischen Studie zur faltbaren, torischen Intraokularlinse (IOL) MicroSil® Toric sollte untersucht werden, wie stabil und zufriedenstellend die Ergebnisse hinsichtlich Visus, Refraktion und Achsenrotation waren. Patienten und Methode: 68 Augen von 48 Patienten aus vier verschiedenen Einrichtungen wurden über einen Zeitraum von drei Monaten nach Kataraktchirurgie untersucht. Ergebnis: Alle Augen erhielten eine individuell angepasste IOL mit Torus zwischen 2,0 und 12,0 D. 68 % der Augen erreichten postoperativ einen unkorrigierten Visus von 0,5 oder besser, 12 % von 1,0 oder besser. Einen korrigierten Visus von 0,5 oder besser erreichten 85 %, einen korrigierten Visus von 1,0 oder besser erreichten 31 %. Der korrigierte Visus verbesserte sich im Mittel um 3 (± 2) Visusstufen. Der unkorrigierte Visus verbesserte sich um 6 Visusstufen im Mittel. Der Anstieg sowohl des korrigierten als auch des unkorrigierten Visus war statistisch signifikant (p < 0,001). Der Effektivitätskoeffizient betrug 1,1 im Median und 1,3 (± 1,5) im Mittel. Die Restrefraktion (im sphärischen Äquivalent) betrug durchschnittlich 0,89 D (± 0,7 D) und wurde im Durchschnitt um 5,14 D (± 4,78 D) reduziert. Der Gesamtastigmatismus wurde ebenfalls statistisch signifikant und klinisch relevant von durchschnittlich 4,6 D (± 2,3 D) auf durchschnittlich 1,12 D (± 0,9 D) reduziert (von 4,0 D auf 1,0 D im Median). 75 % der Augen benötigten postoperativ eine zylindrische Korrektur von weniger als 1,5 D, 95 % von weniger als 2,25 D. Der Hornhautastigmatismus wurde durch die Operation nicht statistisch signifikant verändert (p = 0,435). Der chirurgisch induzierte Astigmatismus nach Naeser betrug 0,7 D im Median. Die Achsenrotation blieb bei 85 % der IOL innerhalb von 5 Grad. 15 % der IOL rotierten mehr als 5 Grad, darunter rotierte nur eine IOL mehr als 10 Grad (Max. 28 Grad). Die Patienten bewerteten ihr Operationsergebnis anhand einer Skala von 1 bis 6 nach dem Schulnotensystem durchschnittlich mit 1,9 (± 1,0; Min. 1,0; Max. 5,0). Es konnten keine klinisch relevanten Korrelationen der klinischen Parameter zur Zufriedenheit festgestellt werden. Zusammenfassung: Faltbare torische IOL mit Z-Haptik ermöglichten entscheidende Verbesserungen hinsichtlich der Refraktion. Diese IOL sind für Augen mit geringen als auch höheren Astigmatismen geeignet. Eine Achsenrotation trat in sehr geringem Maße auf, sodass die Astigmatismuskorrektur weitestgehend berechenbar erzielt werden konnte.