Evaluation of scanning resolution on retinal nerve fiber layer measurement using optical coherence tomography in normal and glaucomatous eyes

PURPOSE: To evaluate the effect of varying the scanning resolution of optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) measurement on diagnostic sensitivity and functional correlation in glaucoma. PATIENTS AND METHODS: 314 eyes from 182 subjects including 107 normal eyes, 83 glaucoma suspect eyes, and 124 glaucoma eyes were included in this cross-sectional study. Standard automated perimetry and OCT measurement of RNFL thickness were performed. Each individual underwent two scanning protocols: (1) fast RNFL thickness (3.4) scan (with resolution of 256 scan points) and (2) RNFL thickness (3.4) scan (with resolution of 512 scan points). RNFL thickness was compared among the groups. Diagnostic sensitivity was evaluated with Receiver Operating Characteristic (ROC) Curve. Relationship between RNFL thickness and visual field mean deviation was examined using linear regression analysis. RESULTS: Measured RNFL thickness using fast RNFL thickness (3.4) scan was significantly higher compared with RNFL thickness (3.4) scan in average, superior, nasal and inferior RNFL in all diagnostic groups. Comparing normal and glaucoma groups, RNFL thickness (3.4) scan produced the largest area under the ROC curve (0.912) based on average RNFL thickness. A stronger correlation between average RNFL and visual field mean deviation was found in RNFL thickness (3.4) scan (R = 0.75, R = 0.56). CONCLUSIONS: Higher resolution RNFL scan provides better diagnostic sensitivity in glaucoma detection and a stronger correlation with visual function.     

The role of Raf-1 in radiation resistance of human hepatocellular carcinoma Hep G2 cells

Development of radiation resistance is one of the major reasons that cancer cells do not respond to radiotherapy and the mechanism for resistance is still not clear. Two sublines of human hepatocellular carcinoma Hep G2 cells were established from cells that survived two different irradiation regimes, 2 Gy for 10 days or 10 Gy for 2 days, respectively. Using MTT assay, the radiation conditioned cells were found to be more resistant to gamma-irradiation and have a greater extent of potentially lethal damage repair (PLDR) for radiation than the parent cells. By Western blot analysis, the radiation-conditioned cells were found to overexpress Raf-1 which is known to regulate the radiation resistance of cells. Inhibition of Raf-1 expression by antisense oligonucleotides increased the radiation sensitivity of the radiation-conditioned cells while inhibitors of Ras (L744,832), PI3K (LY294002) and p38 (SB203580) had no effect. Moreover, antisense Raf-1 oligonucleotides also decreased the radiation induced PLDR capacity of the radiation conditioned cells. It is therefore suggested that Raf-1 may induce radiation resistance through an increase in radiation induced PLDR capacity in Hep G2 cells.     

Primary follicular lymphoma of the small intestine

While nodal follicular lymphoma is prevalent in western countries, primary extranodal presentation is rare. We present the clinico-pathological and radiologic features of a patient with primary follicular lymphoma of the small intestine presenting with intestinal obstruction. This is followed by the discussion on the frequency and staging systems for primary gastrointestinal lymphomas, and the relevance of monoclonal anti-CD20 antibody therapy.     

Human embryonic stem cells: genetic manipulation on the way to cardiac cell therapies

Almost 7 years after their first derivation from human embryos, a pressing urgency to deliver the promises of therapies based on human embryonic stem cells (hESC) has arisen. Protocols have been developed to support long-term growth of undifferentiated cells and partially direct differentiation to specific cell lineages. The stage has almost been set for the next step: transplantation in animal models of human disease. Here, we review the state-of-the-art with respect to the transplantation of embryonic stem cell-derived heart cells in animals. One problem affecting progress in this area and functional analysis in vivo in general, is the availability of genetically marked hESC. There are only a few cell lines that express reporter genes ubiquitously, and none is associated with particular lineages; a major hurdle has been the resistance of hESC to established infection and chemical transfection methodologies to introduce ectopic genes. The methods that have been successful are reviewed. We also describe the processes for generating a new, genetically-modified hESC line that constitutively expresses GFP as well as some of its characteristics, including its ability to form cardiomyocytes with electrophysiological properties of ventricular-like cells.     

Analysis of retinal nerve fiber layer and optic nerve head in glaucoma with different reference plane offsets, using optical coherence tomography

PURPOSE: To evaluate the performance of retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) parameters analyzed with different offsets of reference plane in detecting early glaucomatous changes and in correlation with visual function using optical coherence tomography (OCT). METHODS: This was a cross-sectional study consisting of 41 normal subjects and 30 with early and 40 with advanced glaucoma. RNFL thickness and ONH parameters were measured with reference planes positioned at 95, 150, and 205 microm above the level of retinal pigment epithelium (RPE). Discriminating power for early glaucoma detection and correlation with visual field MD for each parameter at different levels of reference plane were compared by using the analyses of area under the receiver operating characteristic curves (AUCs) and linear regression, respectively. RESULTS: All ONH measurements were significantly different between normal and glaucoma groups, irrespective of the level of reference plane. In normal eyes, changing the reference plane position resulted in significant differences in ONH measurements. Among all the parameters examined, integrated rim volume and RNFL thickness measured at 150 microm above the RPE showed the largest AUC (0.966) for early glaucoma detection, and the strongest correlation with visual function (r = 0.793), respectively. CONCLUSIONS: OCT analysis of the ONH and RNFL is useful for early glaucoma detection. Among the three reference planes examined in this study, measurements analyzed at 150 microm above the RPE demonstrated the best performance for glaucoma detection and correlation with visual function. Compared with ONH measurements, RNFL thickness may be a better indicator, reflecting retinal ganglion cell function and monitoring disease progression.     

Radiation therapy for Bowen's disease of the skin

PURPOSE: To assess the clinical outcome in the radiation therapy (RT) of squamous carcinoma in situ of the skin (Bowen's disease). We focused on the local control rate and the toxicity according to the biologically effective dose (BED). METHODS AND MATERIALS: A retrospective review was performed on 44 patients with Bowen's disease treated at Princess Margaret Hospital from April 1985 to November 2000. RT was the primary treatment for 32 patients, whereas 12 received RT for residual disease after local ablative therapy. Lesions were located as follows: scalp, 9 patients (20%); face, 12 (27%); trunk, 6 (14%), extremity, 12 (27%), perianal, 3 (7%), and penis, 2 (5%). Orthovoltage X-rays were used in the majority (39 of 44, 89%). There was no standard fractionation regimen: some physicians prescribed high doses, as for invasive skin cancer, whereas others prescribed lower doses because of the noninvasive nature of the disease, a sensitive anatomic location (e.g., extremity), or large treatment area. Because of the variations in fractionation regimens, BED was used as a common metric for biologic effect in the comparison of different regimens and analyzed for correlation with recurrence and toxicity. Local control was defined as the lack of persistent or recurrent disease at the treated site for the follow-up period. Grade 4 toxicity was defined as necrosis (cartilage/bone damage) and/or ulceration for a duration of >3 months. RESULTS: The mean patient age was 67.7 years, and the male/female ratio was 29:15. The median pretreatment lesion size was 2.65 cm(2) (range, 0.07-34.56 cm(2)). Complete remission was achieved in 42 patients, with follow-up unavailable for the remaining 2 patients. Subsequently, 3 patients experienced recurrences at 0.2, 1.1, and 1-1.5 years after complete remission. One recurrence was Bowen's disease (local); the others were squamous cell carcinoma (one local, one marginal). Four patients experienced a new squamous lesion at a distant cutaneous site. As of last follow-up, 32 patients (73%) were known to be alive. Median follow-up was 2.6 years (range, 0-11.8 years). All but 3 patients were disease-free at last follow-up, 1 of whom died with distant, but not local disease. The 5-year overall survival rate was 68%. Biologically effective dose was not associated with recurrence. The crude local control rate was 93%. There was a trend toward higher radiation doses for smaller pretreatment tumor and field sizes. The BED did not correlate with Grade 4 toxicity; however, the three cases of Grade 4 toxicity occurred in patients treated with hypofractionated regimens (dose per fraction >4 Gy) for extremity lesions. CONCLUSIONS: Radiation therapy is an effective treatment option for Bowen's disease of the skin. Local recurrences seem to be equally low in patients treated with high- and low-dose regimens. Avoiding hypofractionated regimens (dose per fraction >4 Gy) in extremity locations might reduce the risk of Grade 4 toxicity.