3D MRI-based tumor delineation of ocular melanoma and its comparison with conventional techniques.

The aim of this study is to (1) compare the delineation of the tumor volume for ocular melanoma on high-resolution three-dimensional (3D) T2-weighted fast spin echo magnetic resonance imaging (MRI) images with conventional techniques of A- and B-scan ultrasound, transcleral illumination, and placement of tantalum markers around tumor base and (2) to evaluate whether the surgically placed marker ring tumor delineation can be replaced by 3D MRI based tumor delineation. High-resolution 3D T2-weighted fast spin echo (3D FSE) MRI scans were obtained for 60 consecutive ocular melanoma patients using a 1.5 T MRI (GE Medical Systems, Milwaukee, WI), in a standard head coil. These patients were subsequently treated with proton beam therapy at the UC Davis Cyclotron, Davis, CA. The tumor was delineated by placement of tantalum rings (radio-opaque markers) around the tumor periphery as defined by pupillary transillumination during surgery. A point light source, placed against the sclera, was also used to confirm ring agreement with indirect ophthalmoscopy. When necessary, intraoperative ultrasound was also performed. The patients were planned using EYEPLAN software and the tumor volumes were obtained. For analysis, the tumors were divided into four categories based on tumor height and basal diameter. In order to assess the impact of high-resolution 3D T2 FSE MRI, the tumor volumes were outlined on the MRI scans by two independent observers and the tumor volumes calculated for each patient. Six (10%) of 60 patients had tumors, which were not visible on 3D MRI images. These six patients had tumors with tumor heights < or = 3 mm. A small intraobserver variation with a mean of (-0.22 +/- 4)% was seen in tumor volumes delineated by 3D T2 FSE MR images. The ratio of tumor volumes measured on MRI to EYEPLAN for the largest to the smallest tumor volumes varied between 0.993 and 1.02 for 54 patients. The tumor volumes measured directly on 3D T2 FSE MRI ranged from 4.03 to 0.075 cm3. with a mean of 0.87 +/- 0.84 cm3. The tumor shapes obtained from 3D T2 FSE MR images were comparable to the tumor shapes obtained using EYEPLAN software. The demonstration of intraocular tumor volumes with the high-resolution 3D fast spin echo T2 weighted MRI is excellent and provides additional information on tumor shape. We found a high degree of accuracy for tumor volumes with direct MRI volumetric measurements in uveal melanoma patients. In some patients with extra large tumors, the tumor base and shape was modified, because of the additional information obtained from 3D T2 FSE MR images.

Characterization of a cloned temperature-sensitive construct of the diphtheria toxin A domain.

Our goal was to determine how the DTM mutant construct of the A domain of diphtheria toxin (DTx) causes temperature-sensitive effects in Drosophila and yeast [Bellen, H. J., D'Evelyn, D., Harvey, M., Elledge, S. J. (1992) Development 114, 787-796]. Because DTM fortuitously bears the same point mutation as found in the A chain of CRM197, an ADP-ribosyltransferase (ADPrT)-deficient form of DTx, we hypothesized that the dramatic low-temperature-sensitive effects did not stem from ADP-ribosylation of elongation factor 2 (EF-2). To rule out acquisition of ADPrT activity at low temperatures, we assayed mutant forms of the A domain of DTx produced by in vitro transcription/translation and found that DTM has no ability to ADP-ribosylate EF-2 at 18 or 30 degrees C. Because the DTM gene results in a protein with a 23-amino acid missense carboxy-terminal extension, we also constructed a form without this extension. Assays for nuclease activity revealed that nuclease activity comigrated with the two distinguishable E. coli-cloned mutant proteins DTM and DTM-23, regardless of whether electrophoresis was conducted under denaturing or nondenaturing conditions in gels embedded with DNA. Studies with CRM197 showed that Ca(2+) and Mg(2+) promote single-strand DNA nicks, whereas Mn(2+) promotes double-strand DNA breaks. Evidence that the cation-dependent nuclease and NAD-dependent ADPrT enzymic sites are distinct is that NAD protected only the A domain of DTx from proteolytic cleavage, whereas DNA protected the A domains of both DTx and CRM197. We conclude that the nuclease activity of DTM is responsible for the temperature-sensitive effects associated with its expression in both yeast and Drosophila.

Central corneal thickness of Caucasians, Chinese, Hispanics, Filipinos, African Americans, and Japanese in a glaucoma clinic.

OBJECTIVE: To characterize the central corneal thickness (CCT) of Asian (Chinese, Japanese, and Filipino), Caucasian, Hispanic, and African American patients in a multiethnic glaucoma practice. DESIGN: Retrospective study (chart review). PARTICIPANTS: Glaucomatous (n = 600) and nonglaucomatous (n = 201) eyes of 801 patients examined in a San Francisco glaucoma clinic from June 2002 to April 2004 who met inclusion criteria were included in the study. The 6 racial (ethnic) groups represented in the study were Caucasian (n = 186, 23.2%), Chinese (n = 157, 19.6%), Japanese (n = 121, 15.1%), Hispanic (n = 116, 14.5%), Filipino (n = 114, 14.2%), and African American (n = 107, 13.4%). METHODS: Central corneal thickness was measured by means of ultrasound pachymetry in Asian (Chinese, Japanese, and Filipino), Caucasian, Hispanic, and African American participants with glaucomatous and normal eyes. The relationship between CCT and race was investigated using multivariate regression analyses, controlling for confounders. One eye of each of 801 participants was included for analysis. MAIN OUTCOME MEASURES: Correlation of mean CCT with race, glaucoma diagnosis, age, spherical equivalent, gender, and history of ocular surgery. RESULTS: The mean CCT of all participants was 542.9 mum. Central corneal thicknesses of Chinese (555.6 microm), Caucasian (550.4 microm), Filipino (550.6 microm), and Hispanic (548.1 microm) participants did not significantly differ. The CCT of Japanese participants (531.7 microm) was significantly less than that of Caucasians, Chinese, Filipinos, and Hispanics (all, P< or =0.001) and greater than that of African Americans (P = 0.03). African Americans had a CCT (521.0.0 microm) less than that of all races (P< or =0.05). Glaucoma suspects and patients with normal tension glaucoma (NTG), primary open-angle glaucoma (POAG), pseudoexfoliation glaucoma (PEX), and chronic angle-closure glaucoma (CACG) had corneas significantly thinner than those of normal participants (P< or =0.004), whereas ocular hypertensives had significantly thicker corneas (P<0.0001). Among all participants, decreasing values of CCT were significantly related to older age (P<0.01). Less negative or more positive refractive errors, gender, and history of ocular surgery were not associated with changes in CCT (P = 0.38, P = 0.50, and P = 0.97, respectively). CONCLUSIONS: Studies examining individual Asian subpopulations in isolation suggest that differences in CCT may exist among different Asian groups. The results of this study indicate that CCT does, in fact, vary among Asian subpopulations; Japanese have thinner corneas than Chinese and Filipinos. Caucasians, Chinese, Hispanics, and Filipinos have comparable CCT measurements, whereas the corneas of African Americans are significantly thinner. Additionally, older individuals; glaucoma suspects; and participants with NTG, POAG, PEX, and CACG have thinner corneas. Ocular hypertensives, however, have thicker corneas.

Orbital, middle cranial fossa, and pterygopalatine fossa yolk sac tumor in an infant.

A yolk sac tumor, also known as an endodermal sinus tumor, was diagnosed in a 15-month-old infant who presented with rapidly progressive right eye proptosis. Imaging of the orbits and brain revealed a mass in the right orbit, middle cranial fossa, and pterygopalatine fossa. A lateral orbitotomy was performed to take a biopsy specimen and to partially debulk the tumor secondary to signs of optic nerve compromise. The biopsy specimen revealed a yolk sac tumor, and the patient underwent systemic chemotherapeutic treatment. Because orbital endodermal sinus tumors have been infrequently reported, there are no firm prognostic or treatment guidelines. Our case demonstrates that early recognition, limited orbital debulking, and chemotherapy can have an excellent short-term outcome.