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The treatment of large uveal melanomas poses a therapeutic challenge, due to the expected treatment-related side-effects. After sole radiotherapy the majority of patients are faced with radiogenic complications secondary to the large amount of tumour necrosis. Alternative treatment modalities addressing this issue are transscleral resection in arterial hypotension in anteriorly located tumours and endoresection via pars plana vitrectomy in posteriorly located tumours. A surgical resection treatment was applied in 292 patients with large uveal melanomas. In 150 patients the tumour was treated by transscleral resection and postoperative adjuvant (106)ruthenium brachytherapy and 142 patients were treated by primary proton beam irradiation and secondary endoresection. The mean follow-up time was 3.8 and 2.5 years, respectively. Local tumour control was achieved in 76 % and 98 %, respectively. The 5-year metastatic rates were 28 % and 21 % and eye retention was achieved in 82 % and 97 %, respectively. Surgical resection of uveal melanomas with adjuvant radiotherapy is the treatment of choice in cases of large tumours, avoiding enucleation in the vast majority of cases in the long term, without increasing the incidence of tumour-related risks., ((c) Georg Thieme Verlag KG Stuttgart-New York.)

We evaluated response, progression-free survival (PFS), overall survival (OS), relapse patterns and long-term toxicity of intraocular lymphoma (IOL) patients treated with ifosfamide (IFO) or trofosfamide (TRO). In a prospective single center study, IFO or TRO were given to 10 patients with IOL. The median patient age was 73 (range 46-83) years. Six patients were pretreated with up to four treatment regimens for ocular or cerebral lymphoma, and four were therapy-naive. All patients responded, including nine complete remissions and one partial remission, with a median PFS of 18 (7-36) months. Seven patients relapsed: five in the eye and two in the brain. Median OS was 32 (7-37+) months. No long-term toxicity was observed in patients treated with IFO or TRO alone. IFO or TRO were active and well tolerated in this study. Thus, they may represent suitable combination partners for other cytostatics used for PCNSL and IOL treatment.

Background: Adamantiades-Behçet's disease (ABD) is a multi-system disorder with recurrent oral and/or genital ulcerations, skin lesions and ocular involvement. Eye involvement is a common manifestation that affects the patients' quality of life more than any other. Left untreated, it leads to blindness and often to loss of the eye through secondary complications like phthisis or painful glaucoma. In some cases, such as tractional retinal detachment, secondary glaucoma or secondary cataract formation, intraocular surgery is required., Methods: A prospective study of patients with ocular ABD who underwent intraocular surgery under systemic treatment with interferon-alpha was conducted. From 1999 to 2005, we treated eight eyes from five patients with pars plana vitrectomy (n = 1), phacoemulsification (n = 6) and trabeculectomy (n = 1). The mean follow-up was 49 months (range 5-94 months)., Results: Seven out of eight eyes had better visual acuity following surgery. One eye did not benefit from cataract surgery because of optic nerve atrophy. Only one eye showed prolonged inflammation following phacoemulsification. None of the patients showed a recurrence during follow-up. The failure of conservative glaucoma treatment necessitated trabeculectomy in one eye; the patient has had no further recurrence for 6 years under monotherapy with interferon-alpha., Conclusion: Interferon-alpha is a potent therapy for Adamantiades-Behçet's disease with ocular involvement. It also provides a basis for safe and reliable surgical interventions. In seven of eight eyes, there was no intra- or peri-operative recurrence of inflammation, which is a common complication after these procedures. Only one eye showed acute and prolonged inflammation following cataract surgery.

Background: Pathologists may occasionally have difficulties in reliably assessing the dignity of tumour cells in histological sections, especially in nevi with junctional activity., Patient History: This case history of a boy suffering from an inflammatory juvenile conjunctival nevus (IJCN) is reported with a follow-up period of 25 years. Seven years after first surgical treatment of a histologically proven nevus, a recurrent pigmented lesion within the former operation area aroused the suspicion of it being a malignant melanoma. Logically, a second excision was performed followed by cryotherapy with liquid nitrogen (spray freezing). The histological diagnosis performed by a pathologist resulted in a malignant melanoma. A second recurrent pigmented conjunctival tumour developed fourteen years later. This lesion again aroused another strong clinical suspicion of malignant transformation into a melanoma. However, the histological examination of the biopsy at this time only showed benign nevus cells and areas of conjunctival melanosis without atypia., Discussion: Especially in young patients, IJCN must be regarded as an independent type of nevus, which might lead even experts in ophthalmic pathology to over-diagnose this lesion as a malignant melanoma. This could mean that the wrong therapeutic steps were taken with surgical procedures that cause unnecessary mutilation. A reappraisal of the former histological specimens of the first recurrent tumour by other pathologists came to the conclusion that the initial diagnosis of melanoma could not be maintained. Nevertheless, we also strongly recommend follow-up examinations at regular intervals in cases of IJCN since we are aware of the fact that melanocytic tumours of the conjunctiva behave unpredictably.

The increase of wall shear stress in capillaries by oral administration of the alpha1-adrenergic receptor antagonist prazosin induces angiogenesis in skeletal muscles. Because endothelial nitric oxide synthase (eNOS) is upregulated in response to elevated wall shear stress, we investigated the relevance of eNOS for prazosin-induced angiogenesis in skeletal muscles. Prazosin and/or the NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) were given to C57BL/6 wild-type mice and eNOS-knockout mice for 14 days. The capillary-to-fiber (C/F) ratio and capillary density (CD; no. of capillaries/mm2) were determined in frozen sections from extensor digitorum longus (EDL) muscles of these mice. Immunoblotting was performed to quantify eNOS expression in endothelial cells isolated from skeletal muscles, whereas VEGF (after precipitation with heparin-agarose) and neuronal NOS (nNOS) concentrations were determined in EDL solubilizates. In EDL muscles of C57BL/6 mice treated for 14 days, the C/F ratio was 28% higher after prazosin administration and 11% higher after prazosin and L-NAME feeding, whereas the CD increased by 21 and 13%, respectively. The C/F ratio was highest after day 4 of prazosin treatment and decreased gradually to almost constant values after day 8. Prazosin administration led to elevation of eNOS expression. VEGF levels were lowest at day 4, whereas nNOS values decreased after day 8. In EDL muscles of eNOS-knockout mice, no significant changes in C/F ratio, CD, or VEGF and nNOS expression were observed in response to prazosin administration. Our data suggest that the presence of eNOS is essential for prazosin-induced angiogenesis in skeletal muscle, albeit other signaling molecules might partially compensate for or contribute to this angiogenic activity. Furthermore, subsequent remodeling of the capillary system accompanied by sequential downregulation of VEGF and nNOS in skeletal muscle fibers characterizes shear stress-dependent angiogenesis.

Nitric oxide synthase-1 (NOS-1) can be demonstrated in the sarcolemma region of myofibers in rodent skeletal muscles with the use of NADPH diaphorase histochemistry. Since other, especially intrafibrar enzymes also exhibit NADPH diaphorase activity, we tried to increase the specificity of the histochemical reaction for NOS-1. A qualitative and quantitative analysis was performed on cryostat sections of fast-twitch oxidative myofiber-rich tongue and fast-twitch glycolytic myofibers-rich tibialis anterior muscle derived from C57 mice and NOS-1 deficient knockout mice. All myofibers of both C57 mice and NOS-1 knockout mice contained significant intrafibrar NADPH diaphorase activity which was inhibited to almost background levels when 2 M urea was added to the incubation medium. On the other hand, myofibers of C57 mice but not of NOS-1-deficient knockout mice exhibited NADPH diaphorase activity in their sarcolemma region which was only weakly reduced in the presence of 2 M urea as was demonstrated by image analysis. Quantitative data on the activity of NADPH diaphorase(s) were obtained in situ by photometric analysis of formazan extracted from cryostat sections. The catalytic activity in tongue and tibialis anterior muscle was reduced in presence of 2 M urea to approximately 27% in C57 mice and to 7-17% in NOS-1 knockout mice, respectively. An in vitro NADPH diaphorase assay performed on homogenates of skeletal muscles also revealed an inhibitory effect of 2 M urea in both mouse strains and, additionally, indicated an upregulation of NADPH diaphorase activity in NOS-1 knockout mice. Finally, an immunodepletion analysis demonstrated that NOS-1 comprises 38% of the total NADPH diaphorase activity in tongue and approximately 59% in tibialis anterior muscle in C57 mice. In conclusion, we recommend the addition of 2 M urea to the incubation medium to increase the specificity of the NADPH diaphorase reaction to localise NOS-1 with the use of catalytic histochemistry.