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Biomedical subjects

A Schüler

Publications and source records attributed to A Schüler.

At least 19 recordsLinked to original sources
PubMed2006

[Retinoblastoma].

Retinoblastomas are the most frequent intraocular tumors in childhood. Untreated, the tumor is almost always fatal. Using a multidisciplinary approach combining the efforts of ophthalmologists, radiation oncologists, pediatric oncologists and geneticists a survival rate of more than 95% can be achieved. Molecular genetic research on the origin of retinoblastomas has substantially helped in our understanding of the origin of malignant tumors in general, as well as to the key role of the Rb-1 gene as a tumor suppressor.

Diagnosis, Differential↗
PubMed2006

[Endoresection of large uveal melanomas after pretreatment by single-dose stereotactic convergence irradiation with the leksell gamma knife--first experience on 46 cases].

BACKGROUND: The aim of this non-comparative, consecutive case series is to evaluate the short-term results after endoresection of large uveal melanomas in combination with pretreatment with stereotactic gamma knife radiosurgery. METHODS: Between March 2000 and November 2002, forty-six patients with large uveal melanomas underwent stereotactic radiosurgery followed by endoresection of the tumour via a standard three-port vitrectomy including laser photocoagulation and silicone oil tamponade. The average tumour height was 9.5 mm. The minimum dose delivered to the tumour volume was 25 Gy. RESULTS: The median follow-up time was 410 days. In 40 cases (87 %), the eye was retained with a VA of 20/200 or better in 30 cases (65.2 %) and 20/63 or better in ten cases (21.7 %). In 12 eyes with a follow-up of >/= 0.5 years, the median VA was 20/80 after silicone oil removal and cataract surgery had been performed. Six eyes (13 %) were enucleated due to serious complications caused by the radiosurgery (3 cases) or endoresection (3 cases). In 13 patients (28.2 %), additional major surgery was required. Seven patients developed liver metastases during follow-up and six patients died. No local tumour recurrences were observed. CONCLUSIONS: Eyes with large uveal melanomas can be salvaged by stereotactic radiotherapy followed by endoresection.

Combined Modality Therapy↗
PubMed2005

Spectrum of gross deletions and insertions in the RB1 gene in patients with retinoblastoma and association with phenotypic expression.

Quantitative multiplex PCR and genomic real-time PCR were used to complete an RB1 mutation analysis in 57 of 433 and 72 of 262 patients with hereditary and isolated unilateral retinoblastoma, respectively. These patients were selected because in previous analyses, which focused mainly on the identification of point mutations, no RB1 mutation was found. We identified gross deletions and insertions in peripheral blood DNA from 26 of 57 patients (46%) with hereditary retinoblastoma, and in six of 72 patients (8.3%) with isolated unilateral disease. In addition, we identified 32 somatic mutations in tumor DNA from 31 of 72 patients (43%) with isolated unilateral retinoblastoma. Together with our previous results, we found that gross RB1 alterations were present in the peripheral blood DNA from 65 of 433 (15%) and 17 of 262 (6.5%) patients with bilateral or familial and isolated unilateral retinoblastoma, respectively. Including reported gross deletions, an analysis of the frequency of breakpoints per intron length shows higher densities in introns 13, 16, 23, and 24. Genotype-phenotype analyses showed that on the whole, carriers of gross deletions develop fewer retinoblastomas compared to patients who are heterozygous for other types of RB1 null mutations. Specifically, carriers of cytogenetic and submicroscopic whole gene deletions often have unilateral tumors only. By contrast, almost all patients with gross deletions with one breakpoint in RB1 have bilateral retinoblastoma.

DNA Mutational Analysis↗
PubMed2005

Age at diagnosis of isolated unilateral retinoblastoma does not distinguish patients with and without a constitutional RB1 gene mutation but is influenced by a parent-of-origin effect.

Patients with hereditary cancer are usually diagnosed earlier than patients with non-hereditary tumours. In children with isolated unilateral retinoblastoma, some of whom have a hereditary predisposition, this rule has been subject to debate. We have analysed the clinical manifestation of disease in 188 children with completely resolved mutational status. In 24 (13%) of these patients, testing of blood DNA showed a constitutional RB1 mutation. The distribution of age at diagnosis was not different between patients with and without a constitutional mutation. However, patients with loss of the maternally inherited RB1 allele had an earlier age at diagnosis than patients with loss of the paternally inherited RB1 allele. Our data show that early age at diagnosis does not identify patients with isolated unilateral retinoblastoma that have a higher risk of being carriers of a RB1 gene mutation. Our findings suggest that, at least in some patients, age at diagnosis is modified by a parent-of-origin effect.

Age of Onset↗
PubMed2003

Photodynamic therapy using verteporfin in circumscribed choroidal haemangioma.

AIM: To investigate the safety and efficacy of photodynamic therapy with verteporfin in patients with choroidal haemangioma. METHODS: A non-randomised, prospective clinical investigation of 19 patients with symptomatic circumscribed choroidal haemangioma was performed. Unsuccessful pretreatment (external beam irradiation, laser photocoagulation) was performed in four patients. Patients were included when (1) subretinal exudation involving the fovea, (2) a decrease in visual function, and (3) additional symptoms (for example, metamorphopsia) were present. Photodynamic therapy (PDT) was performed with verteporfin at a concentration of 6 mg/m(2) body surface area and a light dose of 100 J/cm(2) at 692 nm. RESULTS: The mean follow up time was 10.6 months (2-24 months). The mean number of treatment sessions was 2.15 (range 1-5). Visual acuity improved by at least one line in 73.3%, by at least two lines in 42.1%, was stable in 21.1%, and decreased by one line in 5.2% of the patients. Exudation was completely resolved in 94.8% of the cases. Regression of tumour height was documented in all 19 tumours. Patients receiving any pretreatment before PDT, a visual acuity of 0.1 and less, a history of more than 30 months, and no significant response after the first PDT session, did not show any significant improvement. Cox regression analysis revealed that the number of PDT treatment sessions was inversely associated with the improvement in visual acuity of at least two lines. No recurrences and no local or systemic side effects were observed during the follow up time. CONCLUSION: PDT using verteporfin is a safe and effective therapy for the treatment of symptomatic choroidal haemangioma even in tumours located beneath the fovea.

Adult↗
PubMed2002

[Endoscopic resection of malignant melanomas of the uvea after preoperative stereotactic single dose convergence irradiation with the Leksell gamma knife].

In cases of large volume and highly prominent melanomas of the uvea, it is rare for conventional methods of radiation therapy to enable salvage of the globe or even residual functionality of the affected eye. Complications due to the massive amount of accumulated necrotic tissue often necessitate subsequent enucleation of the blinded eye. Tumor-destroying, single-dose convergence irradiation (radiosurgery) of such tumors applied shortly before endoresection can represent a possible therapeutic alternative in these types of cases.

Adult↗
PubMed2001

Marked differences in unilateral isolated retinoblastomas from young and older children studied by comparative genomic hybridization.

Although it is established that the loss of function of both alleles of the RB1 gene is a prerequisite for the development of retinoblastoma, little is known about the genetic events that are required for tumor progression. We used comparative genomic hybridization (CGH) to search for DNA copy number changes in isolated unilateral retinoblastomas. From a series of 66 patients with retinoblastomas with somatic mutations in both RB1 alleles, tumor samples from 13 children with the youngest (2.0-9.8 months) and 13 with the oldest (36.2-84.1 months) age at operation were studied. Loss at 13q14, the location of RB1, was demonstrated in two tumors only. Recurring chromosome imbalances included gains at 6p (11/26), 1q (10/26), 2p (4/26), and 17q (4/26), gains of the entire chromosome 19 (3/26), and losses at 16q (9/26). A commonly gained region at 1q32 was identified. Increased dosage of GAC1, a candidate oncogene located in 1q32, was found in two of four tumors by Southern blot analysis. Comparison of the CGH findings revealed that retinoblastomas from children with an older age at operation showed significantly more frequent (13/13 cases vs 4/13 cases; P = 0.0005) and more complex genetic abnormalities (median, 5 changes/abnormal tumor vs median, 1.5 changes/abnormal tumor; P = 0.003) than retinoblastomas from children with a young age at operation. Gains at 1q, 2p, 17q, of the entire chromosome 19 and losses of 16q were restricted to the older age group. Our results suggest that the progression of retinoblastomas from older patients follows mutational pathways different from those of younger patients.

Blotting, Southern↗
PubMed2001

Acute Budd-Chiari syndrome, portal and splenic vein thrombosis in a patient with ulcerative colitis associated with antiphospholipid antibodies and protein C deficiency.

We report the case of a female patient who had severe thrombotic complications in peripheral (V. jugularis, subclavia, brachialis, poplitea) and visceral (portal and splenic) veins 4 years after the first diagnosis of severe ulcerative pancolitis. A thrombolysis therapy for subclavian and jugular vein thrombosis was performed without complication, but she soon developed acute thrombosis of the hepatic veins (acute Budd-Chiari syndrome). She quickly recovered after liver transplantation and now - 6 years later - she lives a normal life with continuous anticoagulation and medical therapy of the colitis.3 possible causes for the severe coagulation defect in this patient can be supposed: Thrombocytosis, protein C deficiency and an antiphospholipid antibody syndrome.

Adolescent↗
PubMed2000

Significant reduction of the incidence of ovarian hyperstimulation syndrome (OHSS) by using the LHRH antagonist Cetrorelix (Cetrotide) in controlled ovarian stimulation for assisted reproduction.

A prospective, randomized study was performed to compare the efficiency of hormonal stimulation for IVF (in vitro fertilization) in either the long luteal protocol, using the LHRH agonist Buserelin, or the multiple dose LHRH antagonist protocol, using the LHRH antagonist Cetrorelix. Here we present the data on the incidence of ovarian hyperstimulation syndromes (OHSS). 85 and 188 patients were recruited for the stimulation in the LHRH agonist and in the LHRH antagonist protocol, respectively. The groups were comparable regarding anamnestic data. The incidence of WHO degrees II and degrees III OHSS was significantly lower in the Cetrorelix than in the Buserelin group (1.1% vs. 6.5%, p=0.03). Additionally 3 patients in the Cetrorelix group (1.6%) and 5 patients in the Buserelin group (5.9%) did not receive hCG because of a threatening OHSS. The follicle maturation was more homogeneous in the Cetrorelix protocol, with less small follicles on the day of hCG administration but a similar number of oocyte cumulus complexes retrieved. The pregnancy rates per cycle were not significantly different in the Cetrorelix and Buserelin protocol (22% vs. 26%). The Cetrorelix multiple dose protocol is advantageous compared to the long protocol regarding the incidence of OHSS, a potentially life threatening complication of controlled ovarian stimulation.

Buserelin↗
PubMed1999

Uveal melanoma: correlation of histopathologic and radiologic findings by using thin-section MR imaging with a surface coil.

PURPOSE: To evaluate whether the different signal intensities at magnetic resonance (MR) imaging of melanoma are associated with a higher content of melanin. MATERIALS AND METHODS: In a prospective study, MR imaging and ophthalmoscopic examination findings in 42 patients (19 women, 23 men; age range, 30-87 years) with uveal melanoma were compared with histopathologic examination findings obtained after enucleation. MR imaging was performed with 2-mm sections by using a 5-cm surface coil. T1- and T2-weighted images were obtained before and after contrast material administration. RESULTS: In 33 (79%) of the patients, there was homogeneous tumor pigmentation, whereas in nine (21%) patients, there was inhomogeneous bipartite tumor pigmentation. Compared with the histopathologic data, the results of qualitative evaluation were accurate in 29 (58%) of 50 and in 26 (53%) of 49 tumorous areas on T1- and T2-weighted images, respectively. Quantitative evaluation yielded better results, especially at T1-weighted imaging; an 86% correlation was found. Because of methodological reasons, only the superficial pigmentation of inhomogeneous tumors could be evaluated with ophthalmoscopy. CONCLUSION: Thin-section MR imaging of the eye enables an accurate prediction of melanomatous pigmentation with quantitative evaluation of plain T1-weighted images and is superior to ophthalmoscopy in cases of inhomogeneous pigmentation.

Adult↗
PubMed1998

Expression patterns of cyclin D1 and related proteins regulating G1-S phase transition in uveal melanoma and retinoblastoma.

BACKGROUND/AIMS: A checkpoint mechanism in late G1, whose regulation via loss of retinoblastoma protein (pRB) or p16, or overexpression of cyclin D1 or cyclin dependent kinase 4 (CDK4), has been proposed to constitute a common pathway to malignancy. The aims of this study were (a) to compare markers of cell cycle G1-S phase transition in an intraocular tumour with known pRB deficiency (retinoblastoma) and compare it with one with an apparently functional pRB (uveal melanoma); (b) to determine if one of these markers may have a role in the pathogenesis of uveal melanoma; and (c) to determine if there is a difference in cell cycle marker expression following treatment of uveal melanoma and retinoblastoma. METHODS: 90 eyes were enucleated from 89 patients for retinoblastoma (n = 24) or for choroidal or ciliary body melanoma (n = 66). Conventional paraffin sections were assessed for cell type and degree of differentiation. Additional slides were investigated applying standard immunohistochemical methods with antibodies specific for cyclin D1 protein, pRB, p53, p21, p16, BCL-2, and MIB-1. RESULTS: Cyclin D1 protein and pRB were negative in retinoblastoma using the applied antibodies. In contrast, cyclin D1 protein expression was observed in 65% of uveal melanomas; a positive correlation between cyclin D1 cell positivity and tumour cell type, location, growth fraction, as well as with pRB positivity was observed. p53, p21, and p16 could be demonstrated in both tumours. An inverse relation between p53 and p21 expression was demonstrated in most choroidal melanomas and in some retinoblastomas. Apart from a decrease in the growth fractions of the tumours as determined by MIB-1, a significant difference in the expression of G1-S phase transition markers in vital areas of uveal melanoma and retinoblastoma following treatment with radiotherapy and/or chemotherapy was not observed. CONCLUSION: Retinoblastomas and uveal melanomas, two tumours of differing pRB status, differ also in their immunohistochemical pattern for markers of the G1-S phase transition of the cell cycle. The results of the present study support the concept of (a) an autoregulatory loop between pRB and cyclin D1 in tumours with a functional pRB and the disruption of this loop in the presence of pRB mutation, as well as (b) a checkpoint mechanism in late G1, whose regulation via loss of p16 or pRB, or overexpression of cyclin D1 constitutes a common pathway to malignancy. Further, the results raise the possibility of cyclin D1 overexpression having a role in the pathogenesis of uveal melanoma.

Adolescent↗
PubMed1998

[Is combination therapy of chronic hepatitis C with interferon alpha and ribavirin in primary interferon nonresponders indicated?--An analysis of personal experiences and review of the literature].

Combination therapy of chronic hepatitis C with interferon alpha and ribavirin has been proven to be highly effective in naive and relapse patients with two to ten-fold increase of the response rate. However, combination therapy of primary non-responders to interferon alpha is discussed controversially. Therefore, to analyze the response rate to retreatment with a combination therapy with interferon alpha and ribavirin, we compared data of 555 patients described in 23 publications to the data of 16 non-responders treated in our center. The patients received interferon alpha (at least 3 MU tiw) and ribavirin in a dose of 1,000/1,200 mg per day. At the end of treatment 14% of our patients had normal ALT values and were HCV-RNA-negative compared to 34% of all patients described in the literature. In our patients the viral load decreased from 1,110 +/- 670 x 10(3) copies/ml prior to therapy to 300 +/- 480 x 10(3) copies/ml at the end of treatment (p = 0.002). After a follow-up period of six months quantitative RNA-levels rose again to 1,485 +/- 755 x 10(3) copies/ml. Whereas only 7.4% (24/325) of all patients described showed a response with normal ALT values and negative HCV-RNA at the end of follow-up, no sustained response was observed in our patients. In contrast to naive and relapse patients, the response rate of combination therapy in patients previously not responding to interferon alpha alone is only low. Thus, standard regime (IFN 3MU twi plus ribavirin for six months) as a regular therapy for non-responders is not recommended.

Adult↗
PubMed1996

Ionised and total magnesium serum concentrations in renal and hepatic diseases.

Ionised and total magnesium concentrations were determined in the serum of different groups of patients suffering from renal or hepatic diseases. Ionised magnesium was measured by Microlyte 6 (KONE, Espoo, Finland) and total magnesium by atomic absorption spectrometry. In renal insufficiency ionised and total magnesium concentrations were almost equally increased. In proteinuria with a normal glomerular filtration rate, "pseudohypomàgnesaemia" was observed, i.e. decreased total magnesium concentration in parallel with a decreased albumin concentration with no significant change in the concentration of ionised magnesium. Hypermagnesaemia occurred in liver diseases combined with renal insufficiency, whereas "pseudohypomagnesaemia" was most often found in the absence of renal failure. Also treatment with an aldosterone antagonist was associated with a normal ionised magnesium concentration, but the total magnesium concentration was decreased; when additional magnesium was administered, the total magnesium concentration approached a normal value, while ionised magnesium slightly exceeded reference values. Only during cyclosporin treatment did both ionised and total magnesium concentrations become lowered. However, the decrease of total magnesium exceeded that of ionised magnesium due to concomitant hypoalbuminaemia with reduction of the protein-bound fraction. It is concluded that especially low total magnesium concentrations should be investigated by measurement of ionised magnesium to exclude "pseudohypomagnesaemia".

Adolescent↗
PubMed1996

Keratokyphosis in rabbits: a functional and morphologic study.

Keratokyphosis, a "nonfreeze keratomileusis" procedure, was applied in rabbits. The refractive changes were -6.5 +/- 0.7 (SD), -9.5 +/- 2.6, and -13.0 +/- 3.2 D for convex applanation surfaces with a vertex of +100 microns, +125 microns, and +150 microns in the microkeratome and +1.5 +/- 2.0 and +2.5 +/- 2.6 D for concave applanation surfaces with a vertex of -100 microns and -125 microns. The pachymetric corneal changes were +43 +/- 24 microns, +39 +/- 32 microns, and +71 +/- 24 microns for the convex applanation surfaces and -21 +/- 40 microns and -17 +/- 24 microns for the concave. Wound healing was uncomplicated. The scar at the interface was 0-5 microns wide. The mean central density of nerve endings was 1,255 +/- 532/mm2. The endothelial cell size was 25.1% (p < 0.01) greater as measured by specular microscopy than by vital preparation technique; this difference was greater with higher (33.4%) than with lower (18.02%) corneal refraction (p = 0.02). In addition, there was a method-independent correlation (correlation coefficient, -0.63) between endothelial cell count and corneal thickness. This may indicate an increased demand on corneal endothelium in thickened corneas.

Animals↗
PubMed1995

Accuracy of corneal lenticules produced for lamellar refractive corneal surgery.

The layer thickness of the corneal lenticules separated with the Berlin microkeratome and shaped by keratomileusis, keratophakia, keratokyphosis, and intrastromal excimer-laserkeratomileusis was measured with the Universal Measuring Microscope. The vertices of most corneal lenticules showed an undercorrection of the measured values compared with the calculated ones. In keratomileusis, the vertex of the central part of the optical zone of 3.6 mm attained 79 +/- 19 microns instead of 80 microns (99%); in keratophakia, 74 +/- 19 microns instead of 80 microns (93%); in myopic keratokyphosis, 77 +/- 11 microns instead of 105 microns (74%); in hyperopic keratokyphosis, 72 +/- 28 microns instead of 105 microns (69%); and in excimer-laserkeratomileusis, 52 +/- 12 microns instead of 39 microns (120%). The undercorrection of myopic and hyperopic keratokyphosis indicate that this type of nonfreeze keratomileusis is not capable to cut a tissue lens of predicted refraction from compressed corneal tissue. Near symmetrical profiles were achieved in all types of refractive corneal surgery but excimer-laserkeratomileusis had the smallest standard deviation. It was significantly smaller than in hyperopic keratokyphosis (p < 0.05). Intrastromal excimer-laserkeratomileusis of tightly fixed corneal lenticule in the Berlin microkeratome might be the most predictable method of lamellar refractive corneal surgery.

Animals↗
PubMed1995

Indications, results, and complications of refractive corneal surgery with mechanical methods.

Radial keratotomy (RK) incisions permanently weaken the cornea. This structural weakening can cause several complications and side effects, including diurnal fluctuation, progressive hyperopic shift, and the potential for traumatic rupture of the keratotomy scars. Minimally invasive-RK may be a useful alternative to reduce the invasiveness of RK while retaining its efficacy. Mild myopia can be treated by either RK or photorefractive keratectomy. Patients treated by RK in the first eye and photorefractive keratectomy in the second eye preferred the speed of recovery and the clarity of vision with RK. Combining the microkeratome and the excimer laser appears to be an ideal technique to correct high myopia. Laser ablation of the corneal lenticule while securely fixed by the suction ring in the Berlin microkeratome offers the advantage of perfect centration and fixation. Hexagonal keratotomy, used to treat hyperopia, appears to be an unpredictable, unsafe surgical procedure.

Cornea↗
PubMed1994

[Lumbar spondylodiscitis caused by Salmonella enteritidis].

A 19-year-old boy developed paravertebral muscular pain in the lumbar region after an episode of extremely arduous sporting activity, with fever followed by meningism. The cerebrospinal fluid showed a reactive pleocytosis. Initially, no acute inflammatory changes were present on serum and blood analysis, although the erythrocyte sedimentation rate was moderately increased to 25/60 mm. Pyrexia of up to 38.5 degrees C developed 6 days after admission. Because Borrelia IgM and IgG titres were positive, the diagnosis was at first thought to be atypical borreliosis and the patient was treated with antibiotics. However, after a further episode of fever. Salmonella antibody titres, which had initially been normal, rose to 1: 3200 (Salmonella typhi O and H antigens) and 1: 12800 (Salmonella enteritidis, H antigen). At this stage, the erythrocyte sedimentation rate rose to 86/120 mm and the C-reactive protein to 77 mg/dl. The white cell count remained normal throughout. Blood cultures grew Salmonella enteritidis. Abnormalities on bone scintigraphy were confirmed by CT and MRI scans, showing spondylodiscitis of lumbar vertebrae 1 and 2 with limited osteolysis. The lesion resolved completely on 6 week's treatment with ciprofloxacin (200 mg twice a day intravenously) and conservative supportive treatment. Spondylodiscitis is an uncommon complication of salmonellosis and may occur long after the diarrhoea. Cross reactions with Borrelia flagellin antigens may lead to the wrong diagnosis being made.

Adult↗