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Biomedical subjects

A J Mueller

Publications and source records attributed to A J Mueller.

At least 19 recordsLinked to original sources

"Melanoma inhibitory activity" (MIA): a promising serological tumour marker in metastatic uveal melanoma.

PURPOSE: To assess the role of "melanoma inhibitory activity" (MIA) as a potential serum marker for screening and detection of metastatic uveal melanoma. DESIGN: Prospective, clinical study. MATERIAL AND METHODS: Serum samples of 305 patients with uveal melanoma were collected. Serum samples were analysed by a one-step enzyme-linked immunosorbent assay (ELISA) to quantify the MIA serum levels. All patients underwent a standardized echography of the globe to evaluate maximum tumour height and were checked for systemic metastasis of the tumour by liver enzyme tests and ultrasonography of the liver. RESULTS: Twenty patients (6.6%) had proven metastatic disease; eight of them developed it during follow-up. The mean serum concentration of MIA in the 285 patients without metastasis was 6.72 ng/ml, whereas the mean serum concentration of MIA in the 20 patients with metastasis was 13.03 ng/ml (P<0.001). The eight patients who developed metastatic disease during follow-up showed an MIA of 5.92 ng/ml before detection of metastasis and 12.21 ng/ml afterwards (P<0.001). MIA serum levels did neither correlate with the tumour height or to whether local therapy had been applied. CONCLUSION: The elevation of MIA serum levels in patients with metastatic disease from melanoma supports its promising role as a serum marker for monitoring patients with uveal melanoma.

Adult↗

Evidence of a breakdown of corticostriatal connections in Parkinson's disease.

Dendritic spines are important structures which receive synaptic inputs in many regions of the CNS. The goal of this study was to test the hypothesis that numbers of dendritic spines are significantly reduced on spiny neurones in basal ganglia regions in Parkinson's disease as we had shown them to be in a rat model of the disease [Exp Brain Res 93 (1993) 17]. Postmortem tissue from the caudate and putamen of patients suffering from Parkinson's disease was compared with that from people of a similar age who had no neurological damage. The morphology of Golgi-impregnated projection neurones (medium-sized spiny neurones) was examined quantitatively. The numerical density of dendritic spines on dendrites was reduced by about 27% in both nuclei. The size of the dendritic trees of these neurones was also significantly reduced in the caudate nucleus from the brains of PD cases and their complexity was changed in both the caudate nucleus and the putamen. Dendritic spines receive crucial excitatory input from the cerebral cortex. Reduction in both the density of spines and the total length of the remaining dendrites is likely to have a grave impact on the ability of these neurones to function normally and may partly explain the symptoms of the disorder.

Aged↗

[Combined anterior and posterior segment surgery].

AIM: The aim of this study was to review the postoperative findings in the anterior segment after primary vitrectomy performed in combination with cataract surgery. PATIENTS AND METHOD: In a retrospective analysis covering the period from August 2000 to March 2002, we identified 513 consecutive operations on the retina and vitreous body performed primarily to correct various retinal diseases in the ophthalmology department of the Ludwig Maximilian University in Munich. Concomitant cataracts present in all cases were also treated in the one session. Measurement parameters of postoperative irritation of the anterior chamber included anterior chamber cells, Tyndall effect, fibrin, intraocular pressure, and synechiae formation. Various influencing factors were compared to the measurement parameters in univariate analysis. RESULTS: Correlations between some influencing factors and various measurement parameters were statistically significant in univariate analysis. This was not, however, the case for any of the factors in multivariate analysis. CONCLUSION: Performance of the combined operation according to our protocol does not entail any single parameter that indicates a risk for increased postoperative irritation of the anterior chamber.

Anterior Chamber↗

[Stereotactic radiosurgery using the Gamma Knife for large uveal melanomas].

BACKGROUND: We report the results over 3 years with stereotactic radiosurgery using the Gamma Knife for large and unsuitably located uveal melanomas. PATIENTS AND METHODS: A total of 100 patients (51 male, 49 female) have been treated since 1997 following a standardised treatment protocol (outpatient single-shot treatment, maximum dose 50 Gy, tumour margin dose min.25 Gy, retrobulbar anaesthesia alone for globe fixation). The localisation and/or dimension of the tumours did not allow radiation brachytherapy with Ru106 plaques. Of the tumours 18 were located in the ciliary body, 61 were located at the posterior pole, and 21 were located in the mid-periphery. All patients were followed and tested ophthalmologically and neuroradiologically at regular intervals. The 1-year follow-up data were available for 73 patients, 2-year follow-up data for 33 patients and 3-year follow-up-data for 17 patients. RESULTS: Before therapy the maximum apical tumour height (MAH) was median 7.8 mm (95% CI 2.9-12.5 mm): 1 year after treatment (73 patients) the MAH was median 5.7 mm (95% KI 2.4-10.2 mm),2 years after treatment (33 patients) the MAH was median 4.3 mm (95% KI 2.2-8.8 mm),and 3 years after treatment (17 patients) the MAH was median 4.6 mm (95% KI 2.4-8.5 mm). All differences to the MAH of the corresponding patients before treatment were statistically significant (paired t-test). Within the first year after treatment seven patients were enucleated due to a painful secondary glaucoma,within the second year after radiation two patients (one tumour recurrence, and one secondary glaucoma) and within the third year one more patient (tumour recurrence) was enucleated. CONCLUSIONS: Our 3-year results demonstrate that radiosurgery using the Gamma Knife is beneficial in achieving a local tumour control in 98% of eyes with large and unsuitably located uveal melanomas. The risk for a secondary enucleation is highest in the first year after treatment with a favourable overall rate of 10%. Due to the excellent local tumour control rate we decreased the maximum dose to 40 Gy (min.tumour margin dose 20 Gy) in the subsequently treated patients.

Ciliary Body↗

[Regression of an uveal metastatic tumor from breast cancer during chemotherapy--a case report].

BACKGROUND: Choroidal metastases generally respond well to radiation treatment. However, a deterioration of visual acuity after radiation must be taken into account in lesions involving the optic nerve. In these cases, alternatives to radiation, which is a palliative treatment in most cases anyway, should be considered. MATERIAL AND METHODS: We present the clinical and echographic findings of a case of a 39-year-old patient with choroidal metastasis from breast carcinoma. RESULTS: We observed a regression of the metastasis and an improvement of visual acuity from 0.2 to 1.0 under systemic chemotherapy. Echography showed a decrease of tumor height and increasing reflectivity indicating progressive scarring of the lesion. Up to now, the patient has survived 9 years after initial diagnosis. CONCLUSIONS: Especially in cases in which a deterioration of visual acuity after radiation must be expected, the follow-up during systemic chemotherapy alone might be considered an alternative option, as it not only might preserve vision, but also allows an "in vivo" monitoring of the success of the chemotherapy applied.

Adult↗

[Relative contraindication of latanoprost in iris tumors with secondary glaucoma].

INTRODUCTION: Melanocytic iris tumors are often benign and merely require regular follow-up. Evident growth, increasing pigmentation and secondary glaucoma, however, are possible signs of a malignant transformation. PATIENT: We present a 34-year-old male patient showing a localized, mildly prominent hyperpigmentation of the right iris expanding over 2 h. The lesion had been known since childhood and increasing intraocular pressure (IOP) was treated with timolole, dipivefrin and finally with latanoprost. PROGRESSION: The patient was seen for the first time at our hospital 4 years previously, presenting an IOP of 28-30 mmHg of the right eye. The tumor had developed marked heterochromia and a nodular prominent surface, the chamber angle was partly closed and completely hyperpigmented. The ciliary body was not affected by the tumor and standard ultrasound revealed a maximum thickness of 1.2 mm. Over the last 4 years, IOP and heterochromia had increased but without growth of the tumor. An excisional biopsy of the prominent portion was refused by the patient. DISCUSSION: The melanocytic iris tumor described shows malignant characteristics such as progressive heterochromia and secondary glaucoma. However, increasing iris pigmentation can also be caused by topical application of latanoprost. With the evidence of absent tumor growth, there is no reason to suggest malignant degeneration. Generally, in iris naevi or tumors requiring regular follow-up, application of latanoprost should be avoided in order not to conceal the alteration of pigmentation as possible malignant conversion.

Adult↗

[Correlation between ICG angiography verified networks in uveal melanomas and rate of tumor regression after brachytherapy].

INTRODUCTION: The post-irradiation regression rate of uveal melanomas is a prognostically significant factor for the development of metastases. Other predictive factors for metastases are histological networks which are imagable with confocal ICG angiography. The purpose of this study was to evaluate a possible connection of networks in the ICGA and tumor regression rates. METHODS: We compared the post-irradiation regression rates (as %) in 20 patients 1 year after brachytherapy with networks identified in pre-treatment indocyanine green angiography (ICGA). The ICG angiography was performed before irradiation, 10 patients were irradiated with Ru-106 and 10 were irradiated with Id-125. RESULTS: The mean preoperative maximum apical height was 5.2 mm [SD: 1.5 mm; Ru106 group: 5.7 mm (SD: 1.0 mm); Id-125 group: 5.0 mm (SD: 1.9 mm)]. In 11 patients (55%) (Ru-106: 5; Id-125: 6) we found networks in the preoperative ICG. The mean regression rate in tumors with networks was 51.3% (SD: 14.7%) and 28.0% (SD: 16.4%) in the group without networks. The difference between both groups was statistically significant (p = 0.003, Mann-Whitney test). No statistically significant difference in the regression rates was found between the two groups of brachytherapy Ru-106 and Id-125 (p = 0.165, Mann-Whitney test). DISCUSSION: Highly proliferative tumors are known to be more sensitive to irradiation. This may be one reason why tumors with a rapid post-irradiation regression are the more aggressive ones with regard to later development of metastases. Histopathological networks are also known to be a strong indication of more aggressive, metastasizing tumors. These networks are also imagable in ICG angiography. Our observation emphasizes a connection between networks in ICG angiography and regression rates of uveal melanomas after brachytherapy.

Adult↗

[The Munich/San Diego/Iowa City Collaboration (MuSIC). MuSIC Report I: Design , characteristics of the collective and preliminary results].

BACKGROUND: We have previously shown that histologically described microcirculation patterns (MCP) can be visualized with indocyanine green (ICG) angiography. We have designed a prospective study to evaluate the prognostic value of these angiographically imaged MCP in small choroidal melanocytic lesions. In this report we describe the design of the study, characterize the patient collective, and present the first results. PATIENTS AND METHODS: In this prospective nonrandomized observational study, unilateral choroidal melanocytic lesions with 1.5-5.5 mm maximum apical height are observed until growth is determined according to defined criteria. Variables are demographic parameters, subjective symptoms, subretinal fluid, location and dimension of tumor, hemorrhage, color, orange pigment, and MCP determined by ICG angiography: normal, straight, parallel without crosslinking, parallel with crosslinking, arcs without branching, arcs with branching, loop, and network. RESULTS: Seventy patients (22 males, 48 females; age: 33-88 years, median: 64 years) have been included up to now: 19 tumors showed growth so far (time to growth: 51-946 days, median: 127 days). The following parameters were statistically significantly correlated with time to tumor growth: flashes (p = 0.082), orange pigment (p = 0.012), subretinal fluid (p < 0.001), maximum basal tumor diameter (p = 0.001), maximum apical tumor height (p < 0.001), parallel with crosslinking (p < 0.001), arcs with branching (p = 0.006), loop (p < 0.001), and network (p < 0.001). Of these, complex MCP (parallel with crosslinking, arcs with branching, loop and/or network) showed the strongest correlation with time to tumor growth in a Cox regression model. Based on our data, the positive predictive value of imaging complex MCP (for growth within 12 months) is 78% and the negative predictive value is 98%. CONCLUSION: Our patient collective demonstrates comparable prognostic parameters for time to growth as described in the literature. In addition, the ICG angiographic detection of complex MCP is more strongly predictive of the time to growth than other clinically determinable factors. Thus, we recommend this examination for patients with small choroidal melanocytic lesions, if the patient is to be counseled regarding the likely biologic behavior of his tumor.

Adult↗

Melanoma inhibitory activity: a novel serum marker for uveal melanoma.

The aim of this study was to evaluate the tumour-associated antigen melanoma inhibitory activity (MIA) as a potential novel serological tumour marker in primary and metastatic uveal melanoma in both the laboratory and the clinical setting. In the laboratory setting, immunohistochemical staining with MIA antibody was performed in paraffin-embedded tissues from six amelanotic uveal melanomas and eight metastatic lesions of uveal melanomas. In the clinical setting, serum samples of 139 patients with uveal melanoma were examined; eight of these patients had overt metastatic disease. Sixty-one initially metastatic disease-free patients were followed over time (median follow-up 240 days, 95% confidence interval 60-883 days) and MIA levels were assessed repeatedly. A one-step enzyme-linked immunosorbent assay was used to quantify the MIA serum levels. In the laboratory setting, five of the six primary uveal melanomas and seven of the eight metastatic lesions stained immunohistologically positive for MIA. In the clinical setting, the 131 patients without overt metastatic disease demonstrated a median serum concentration of MIA of 6.6 ng/ml. In the eight patients with overt metastatic disease, the median serum concentration of MIA was 26.28 ng/ml. This difference was highly statistically significant (P < 0.001, analysis of variance). During follow-up, three initially metastatic disease-free patients developed overt metastatic disease, and the MIA level increased from a median of 6.6 ng/ml before to 29.2 ng/ml after clinical detection of metastatic disease. In the 58 other patients, the serum level remained stable during the entire follow-up period. In conclusion, MIA is expressed in primary and metastatic lesions of uveal melanomas, and a statistically significant elevation in MIA serum levels in patients who develop metastatic disease due to uveal melanoma indicates its promising role as a serum marker for monitoring uveal melanoma patients for metastasis.

Adult↗

Interobserver and intraobserver variability of measurements of uveal melanomas using standardised echography.

AIMS: To report on the intraindividual and interindividual variability of tumour size (height and base diameter) measurements using standardised echography in a masked prospective study. METHODS: 20 consecutive eyes of 20 patients were examined on four different visits by three experienced examiners using standardised echography. As common in standardised echography, tumour height was evaluated with A-scan technique, while transverse and longitudinal base diameter were calculated with B-scan. RESULTS: Tumour height measurements using A-scan were more accurate than base diameter measurements using B-scan. The standard deviation for tumour height over all visits/measurements was 0.18 mm (A-scan), 0.79 mm for transverse, and 0.69 mm for longitudinal base diameters (B-scan). The interclass correlation coefficient (ICC) was much higher for tumour height measurements with A-scan (0.7735 for three examiners on one visit) than for transverse (0.6563) or longitudinal (0.4522) base diameter measurements with B-scan techniques. CONCLUSIONS: A-scan techniques for tumour height measurements provide very reproducible results with little intraindividual and interobserver variability. As B-scan techniques for tumour base evaluation are less accurate they should be used for topographic and morphological examinations.

Adult↗

[3-D ultrasound. Initial experiences in various eye diseases].

BACKGROUND: Studies have confirmed three-dimensional (3-D) ultrasound as a practical diagnostic tool in examining the eye and orbit and suggest its routine clinical use. MATERIALS AND METHODS: 3-D ultrasound was prospectively performed in 46 patients (46 eyes) with various ocular diseases. In six large choroidal melanomas the tumor volume were measured by 3-D ultrasound and compared to that measured by MRI and to that calculated by a theoretical formula. To assess the reproducibility of volumetry by 3-D ultrasound the volumes of such three intraocular tumors were measured ten times using ten different virtual sectioning planes and a section thickness of 0.5 mm and/or 1.0 mm. RESULTS: 3-D ultrasound allows the precise assessment of complex three-dimensional structures. Choroidal melanoma volumes measured by 3-D ultrasound, MRI, and theoretical calculation were in the same range. CONCLUSION: Intraocular tumor volume can be measured well by 3-D ultrasound,which may be of clinical importance in follow-up examinations.

Choroid Neoplasms↗

Macular hole surgery in an eye with an optic pit.

PURPOSE: To report an eye with a full-thickness macular hole and an associated optic pit and the noteworthy intraoperative findings. METHODS: Case report. A 56-year-old woman presented with visual acuity LE: 20/100, a full thickness macular hole, and an optic pit. Optical coherence tomography and ophthalmic examination were performed preoperatively and postoperatively. RESULTS: Although usually a macular hole associated with an optic pit tends to be a lamellar and characterized by outer layer defects within preexisting macular detachments or schisis-like cavities, this type of macular hole was not presented in this case. Although the macular hole resembled the idiopathic type on clinical examination as well as on optical coherence tomography, it could only be closed in the third surgical attempt after using silicone oil as a long-standing tamponade. Peeling of an epiretinal membrane or the internal limiting membrane was not possible during any of the three surgeries. CONCLUSION: Our observations suggest that in cases of macular hole in association with optic pit, instillation of silicone oil should be considered in the first surgical procedure, especially if no epiretinal membrane or internal limiting membrane peeling is possible intraoperatively.

Diagnostic Techniques, Ophthalmological↗

Imaging the microcirculation of untreated and treated human choroidal melanomas.

INTRODUCTION: Histologically demonstrable microcirculation patterns (microcirculation pattern) of human choroidal melanomas have prognostic significance for the patient. We report on our experience in imaging these microcirculation pattern in vivo using simultaneous confocal Fluorescein (FA)- and Indocyaninegreen (ICG) angiography before and after brachytherapy. PATIENTS AND METHODS: The simultaneously procured confocal FA- and ICG angiograms of 50 patients with untreated choroidal melanomas were studied for the visibility of microcirculation pattern. Patients were also followed with simultaneous FA/ICG after brachytherapy. RESULTS: Confocal FA disclosed signs of tumor vascularization in 12 (24%) of the 50 examined patients but microcirculation pattern only in 3 patients (6%). In contrast, simultaneously obtained confocal ICG disclosed microcirculation pattern in 47 patients (94%). In 10 (77%) of the 13 patients the tumor microcirculation changed considerably after brachytherapy: Distortion, thickening, thinning, as well as complete obliteration of vessels could be observed. CONCLUSION: Histologically demonstrated microcirculation pattern can be imaged in vivo. This offers the possibility to assess the likely biologic behavior of the individual tumor without the need for obtaining a cytologic or histologic specimen via enucleation or fine-needle biopsy. Confocal ICG angiogiography images microcirculation pattern better than FA which can be explained by the different absorption-, fluorescence- and exudation-characteristics ICG. Follow-up with confocal ICG of choroidal melanomas after brachytherapy shows different features and allows for visualization of the microcirculation reaction to the treatment which might be a useful tool for studying the effects of future anti-angiogenesis based tumor therapies.

Adult↗

[Diagnosis and differential diagnosis of the combined hamartoma of the retina and retinal pigment epithelium].

BACKGROUND: The combined hamartoma of the retina and the retinal pigment epithelium (CHR-RPE) is an important differential diagnosis of retinal and choroidal diseases with variable degrees of pigmentation. PATIENTS: The clinical picture and typical fluorescence angiography findings of two adult patients who were first diagnosed to have a combined hamartoma of the retina and retinal pigment epithelium are presented. The referral diagnosis macular pucker and malignant melanoma of the choroid, respectively, are discussed regarding severe therapeutic interventions such as pars plana vitrectomy with membrane peeling (macular pucker), and radiotherapy, or enucleation (malignant melanoma of the choroid) as well as other important differentials. RESULTS: The combined hamartoma of the retina and the retinal pigment epithelium is a benign congenital, mostly unilateral retinal lesion. The presenting symptom is a painless, unilateral, often silent loss of vision. Histologically, three cell populations can be identified: glial, vascular, and pigmented cells. Variations in composition of these three cell types are responsible for the heterogeneous clinical picture and thus diagnostic challenges. The greyish retinal tumor located peripapillary in most cases with varying degrees of pigmentation and surrounding vascular tortuosity can result in secondary changes at the vitreoretinal interface with deterioration of vision. Combined fluorescein-/indocyaningreen angiography and ultrasound are crucial for diagnostic evaluation. Documentation and regular clinical follow-up examinations are essential for successful management of this disorder. CONCLUSION: Recognition of this rare clinical entity is crucial for administering the appropriate therapy.

Adult↗

[Multifactorial analysis of therapeutic outcome of pseudophakic retinal detachment surgery].

BACKGROUND: Pseudophakic retinal detachment is one of the most severe complications after cataract surgery and is a common cause of permanently reduced visual acuity. We evaluated parameters predicting reduced functional outcome by a model of stepwise regression analysis. PATIENTS AND METHODS: A series of 102 consecutive patients with pseudophakic retinal detachment were analyzed for various parameters regarding cataract surgery, retinal surgery, and retinal detachment features. First, univariate analysis determined the correlations with reduced functional outcome. Secondly, a stepwise regression model analyzed statistically significant variables for their predictive value of a reduced visual outcome. RESULTS: The overall reattachment rate was 99%. In 69% of the patients there was an improvement of more than two lines at the end of the follow-up period. The most predictive factors for reduced functional outcome were the need for a silicone oil tamponade and the visual acuity prior to retinal detachment surgery. When silicone oil tamponade was not needed, the requirement of more than two retinal surgeries was the most predictive factor for reduced visual outcome. CONCLUSION: In our series the strongest predictive factors for a reduced functional outcome were the necessity of silicone oil, reduced visual acuity at the time of retinal detachment, and the requirement of more than two retinal surgeries. These findings suggest that first-line procedures should not be necessarily minimally invasive measurements but rather procedures that result in a stably attached retina in the first instance without permanent silicone oil tamponade, even if this first operation consists of an extended pars plana vitrectomy.

Adult↗