Late postoperative opacification of MemoryLens hydrophilic acrylic intraocular lenses: case series and review

PURPOSE: To report clinical and spectrographic analyses of 2 explanted hydrophilic acrylic intraocular lenses (IOLs). SETTING: John A. Moran Eye Center, Salt Lake City, Utah, USA, and Johannes Gutenberg-University, Department of Ophthalmology, Mainz, Germany. METHODS: We report 6 cases of opacification of MemoryLens IOLs (Ciba Vision) that occurred approximately 2 years after implantation. The anterior and posterior surfaces of the IOLs had a white, frosted appearance, and the IOLs' interior looked brown, similar to the appearance of a brunescent cataract. Two of the IOLs were explanted because of a significant decrease in visual acuity. The IOLs were sent for further clinicopathologic analysis including scanning electron microscopy and energy dispersive x-ray spectroscopy (EDX). RESULTS: Microscopic analysis revealed multiple, fine, granular deposits of various sizes on the surface of the lens optics. The EDX analysis showed the presence of calcium within the deposits. CONCLUSIONS: Our cases show that hydrophilic acrylic IOLs can opacify even years after implantation. Analysis of the explanted IOLs revealed calcification.     

Chemokines and chemokine receptors as targets in the therapy of psoriasis

Chemokines are members of a superfamily of small, cytokine-like, chemotactic proteins that have recently been shown to critically regulate leukocyte trafficking. Accumulating evidence indicates that the chronically relapsing inflammatory skin disease psoriasis represents a T cell-mediated disease. Thus, the understanding of the underlying mechanisms of memory T cell homing to the skin may provide promising targets for the development of novel therapeutics. Here results of recent studies associating chemokines with a psoriatic phenotype and delineating their role in the recruitment of memory T cells to the skin are discussed.     

Gallium in cancer treatment

The trivalent gallium cation is capable of inhibiting tumor growth, mainly because of its resemblance to ferric iron. It affects cellular acquisition of iron by binding to transferrin, and it interacts with the iron-dependent enzyme ribonucleotide reductase, resulting in reduced dNTP pools and inhibition of DNA synthesis. The abundance of transferrin receptors and the up-regulation of ribonucleotide reductase render tumor cells susceptible to the cytotoxicity of gallium. Remarkable clinical activity in lymphomas and bladder cancer has been documented in clinical studies employing intravenous gallium nitrate, which is currently being re-evaluated in non-Hodgkin's lymphoma. An improved therapeutic index is expected to result from prolonged exposure to low steady-state plasma gallium levels. Attempts to accomplish this by oral administration of gallium chloride failed because of insufficient intestinal absorption. Complexation of gallium with ligands, which stabilize gallium against hydrolysis and facilitate membrane permeation, has been recognized as a promising strategy for overcoming these limitations. Two such gallium complexes, namely tris(3-hydroxy-2-methyl-4H-pyran-4-onato)gallium(III) (gallium maltolate) and tris(8-quinolinolato)gallium(III) (KP46), which both exhibit high bioavailability when administered via the oral route, are currently being evaluated in the clinical setting.     

Capecitabine in hormone-resistant metastatic prostatic carcinoma - a phase II trial

The objective of the trial is to evaluate the efficacy of capecitabine in patients with metastatic hormone-resistant prostate carcinoma (HRPC), in terms of prostate-specific antigen (PSA) response and clinical benefit (decrease of pain or analgesic score) and its safety profile. In all, 25 patients with HRPC were enrolled on a phase II trial of capecitabine (Xeloda) at a dose of 1250 mg m(-2) orally twice daily on days 1-14 every 21 days. The inclusion criteria were PSA serum levels >3 x upper limit of normal, a WHO performance status 0-2, age <85 years and adequate bone marrow, liver and renal function. In patients with grade 2 or higher haematological toxicity on day 1 of the treatment cycle, therapy was first delayed, and then continued at a lower dose. Trial end points were PSA response and clinical benefit defined by quality of life (QL) data and analgesic consumption. The median age of patients was 70 years (range 54-85 years). A median of three cycles of capecitabine was administered (range 1-8). PSA response was observed in three patients (12%, 95% CI 3-31%), with times to tumour progression of 18, 21 and 35 weeks, respectively. In these patients, the response durations were 12, 17 and 32 weeks, respectively. Minor PSA regression was also seen in two further patients. The median time to tumour progression of all patients was 12 weeks (95% CI 9-15 weeks). Haematological toxicity was minor, with leukopenia grade 3 observed in one patient. There were three deaths during trial treatment, respectively, due to sepsis following mucositis and leukopenia, presumed sepsis with mucositis induced by chemotherapy and concomitant radiotherapy and cerebral dysfunction progressing to coma. Hand-foot syndrome grades 2 and 3 were observed in four patients each. Clinical benefit was observed in five patients (20%, CI 7-41%). Based on toxicity data, we recommend a lower starting dose of 1000 mg x m(-2) orally twice daily. While capecitabine has some activity in HRPC, as suggested by observed PSA responses, we conclude that it is not worthwhile to investigate capecitabine monotherapy in a phase III trial. Combinations of capecitabine with other agents, such as vinorelbine or docetaxel, may prove to be more effective.     

The influence of Ras pathway signaling on tumor radiosensitivity

Radiotherapy is used to treat approximately 60% of solid tumors in the US. The relative radiosensitivity of these tumors can have a significant impact upon local control. One factor that has been shown to contribute to the increased survival of tumor cells is the activation of signaling pathways in which oncogene products play a central role. The Ras oncoprotein family, comprised of H-, K-, and N-Ras are frequently activated by mutation in certain tumors such as pancreatic and non-small cell lung cancers and are activated by receptor tyrosine kinase activity in an even wider range of tumor types. The role of ras mutation and more recently Ras signaling has been an area of intense study in both radiobiology and tumor biology in general. In this review, we focus on findings from our lab and others that led to the current hypotheses relating to the role of Ras signaling in tumor radiation survival and the strategies used to block Ras activation. We will also point out new means of studying the contribution of Ras and Ras pathway components that could contribute to defining new targets for inhibition in the context of radiation therapy.     

Low occurrence of familial neuroblastomas and ganglioneuromas in five consecutive GPOH neuroblastoma treatment studies

Familial neuroblastoma is of special interest in view of the oncogenesis of this tumour with its early manifestation in childhood. The inheritance seems to follow an autosomal-dominant Mendelian trait with incomplete penetrance. Familial neuroblastomas and ganglioneuromas have not been reported in detail within large treatment studies. A retrospective clinicopathological survey of patients reported to the German neuroblastoma treatment studies over 24 years was performed. Among 2863 patients (2752 neuroblastomas, 111 ganglioneuromas) included in five consecutive trials, only 22 hereditary cases in ten families were observed. Neuroblastomas were found in 18 patients and ganglioneuromas in four, accounting for less than one percent of all cases. Six patients with neuroblastomas had localised disease, seven had stage 4, three had stage 4S, and stage was unknown in two patients. In four families, two generations were affected, with ganglioneuromas occurring in the parental generation in two families. Two families had three affected patients. Contrary to previous reports, age distribution and number of primary tumours in patients with familial tumours were not significantly different from patients with sporadic tumours. The outcome of both groups was comparable. These data confirm the low prevalence of familial neuroblastoma and may help in counselling the affected families.