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Biomedical subjects

Susan Schneider

Publications and source records attributed to Susan Schneider.

At least 19 recordsLinked to original sources

Ranibizumab versus verteporfin for neovascular age-related macular degeneration.

BACKGROUND: We compared ranibizumab--a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A--with photodynamic therapy with verteporfin in the treatment of predominantly classic neovascular age-related macular degeneration. METHODS: During the first year of this 2-year, multicenter, double-blind study, we randomly assigned patients in a 1:1:1 ratio to receive monthly intravitreal injections of ranibizumab (0.3 mg or 0.5 mg) plus sham verteporfin therapy or monthly sham injections plus active verteporfin therapy. The primary end point was the proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months. RESULTS: Of the 423 patients enrolled, 94.3% of those given 0.3 mg of ranibizumab and 96.4% of those given 0.5 mg lost fewer than 15 letters, as compared with 64.3% of those in the verteporfin group (P<0.001 for each comparison). Visual acuity improved by 15 letters or more in 35.7% of the 0.3-mg group and 40.3% of the 0.5-mg group, as compared with 5.6% of the verteporfin group (P<0.001 for each comparison). Mean visual acuity increased by 8.5 letters in the 0.3-mg group and 11.3 letters in the 0.5-mg group, as compared with a decrease of 9.5 letters in the verteporfin group (P<0.001 for each comparison). Among 140 patients treated with 0.5 mg of ranibizumab, presumed endophthalmitis occurred in 2 patients (1.4%) and serious uveitis in 1 (0.7%). CONCLUSIONS: Ranibizumab was superior to verteporfin as intravitreal treatment of predominantly classic neovascular age-related macular degeneration, with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 1 year. (ClinicalTrials.gov number, NCT00061594 [ClinicalTrials.gov].).

Aged↗

Metabolic engineering of Pseudomonas putida for methylmalonyl-CoA biosynthesis to enable complex heterologous secondary metabolite formation.

An operon consisting of three open reading frames, annotated in silico as methylmalonyl-CoA (mm-CoA) epimerase, mm-CoA mutase (MCM), and meaB, was identified in the sequencing project of the myxobacterium Sorangium cellulosum So ce56. This putative MCM pathway operon was subcloned from a bacterial artificial chromosome by Red/ET recombineering onto a minimal replicon derived from p15A. This plasmid was modified for integration and heterologous expression in Pseudomonas putida to enable the production of complex secondary metabolites requiring mm-CoA as precursor. Methylmalonate was identified in the recombinant P. putida strain by an analysis method based on gas chromatography/mass spectrometry. The engineered strain is able to synthesize polyketides requiring mm-CoA as an extender unit, which was demonstrated by the production of myxothiazol after integration of the biosynthetic gene cluster into the chromosome, followed by induction of expression.

Acyl Coenzyme A↗

A recombineering pipeline for functional genomics applied to Caenorhabditis elegans.

We present a new concept in DNA engineering based on a pipeline of serial recombineering steps in liquid culture. This approach is fast, straightforward and facilitates simultaneous processing of multiple samples in parallel. We validated the approach by generating green fluorescent protein (GFP)-tagged transgenes from Caenorhabditis briggsae genomic clones in a multistep pipeline that takes only 4 d. The transgenes were engineered with minimal disturbance to the natural genomic context so that the correct level and pattern of expression will be secured after transgenesis. An example transgene for the C. briggsae ortholog of lin-59 was used for ballistic transformation in Caenorhabditis elegans. We show that the cross-species transgene is correctly expressed and rescues RNA interference (RNAi)-mediated knockdown of the endogenous C. elegans gene. The strategy that we describe adapts the power of recombineering in Escherichia coli for fluent DNA engineering to a format that can be directly scaled up for genomic projects.

Animals↗

Eyelid-sparing adjuvant radiation therapy for renal cell carcinoma.

PURPOSE: To describe the use of debulking surgery with adjuvant external beam irradiation as an eyelid-sparing treatment for renal cell carcinoma. DESIGN: Interventional case report. METHODS: A 63-year-old male presented with a right upper lid tumor. He had a history of renal cell carcinoma and pulmonary metastasis treated with surgery and systemic chemotherapy. The eyelid tumor was biopsied, followed by debulking surgery and external beam radiation therapy to treat this metastatic tumor. RESULTS: Histopathological evaluation of the excised tumor revealed a metastatic renal cell carcinoma, clear cell type. At 4 months' follow-up, he had no evidence of recurrence or radiation oculopathy. He was pleased with his cosmetic result. CONCLUSIONS: Meta static renal cell carcinoma presenting in the eye and orbit can be the initial manifestation of the primary tumor. It is important to include this tumor in the differential diagnosis of recurrent eyelid lesions. Debulking surgery followed by external beam radiation therapy can be used to control the tumor with an eyelid-sparing cosmetic result.

Biopsy↗

Cardiopulmonary bypass for a coronary artery bypass graft patient with heterozygous protein C deficiency and protein S deficiency.

Cardiopulmonary bypass (CPB) poses great risks for hypercoagulable patients and requires management techniques to ensure an optimal outcome free from thrombotic events. This case report reviews perfusion management techniques that may contribute to a safer CPB experience for a patient deficient in both protein C and protein S. A patient with heterozygous protein C deficiency is at increased risk of thrombosis, especially in the venous circulation. Since it is an essential cofactor for activated protein C, deficiency of free protein S is also linked to a hypercoagulable condition. A 52-year-old male presented to our institution with a past medical history of hypercoagulable state, multiple deep vein thromboses, pulmonary embolisms, and stroke. He was scheduled for two-vessel coronary artery bypass graft surgery to be followed by right carotid endarterectomy (RCEA) before discharge. The anesthesia and perfusion teams worked closely together to ensure that fresh frozen plasma (FFP) was given intraoperatively at appropriate times. Heparin dose response and protamine dosage was determined with hemostasis management system (HMS) analysis. The closed CPB circuit and cannulae were Carmeda bonded. Rapid autologous priming, along with the use of a hemoconcentrator, kept the hematocrit above 21 during CPB. Zero-balance ultrafiltration and leukocyte depletion were initiated during rewarming to aid in attenuation of the inflammatory response. To conserve coagulation factors, all pump blood was ultrafiltrated post-CPB and returned to the patient. Laboratory samples drawn on postoperative day (POD) one measured normal protein C activity with subnormal protein S activity. On POD six, the patient underwent RCEA and he was discharged on POD eight without complications.

Cardiopulmonary Bypass↗

Adenocarcinoma arising from congenital hypertrophy of the retinal pigment epithelium.

BACKGROUND: Adenocarcinoma of the retinal pigment epithelium (RPE) is a rare primary malignant intraocular neoplasm. We report a histopathologically confirmed case of adenocarcinoma of the retinal pigment epithelium arising from congenital hypertrophy of the retinal pigment epithelium (CHRPE). METHODS: The clinical features, surgical management, and histopathological features of a melanotic tumor arising from CHRPE are presented. The tumor was excised by transcleral resection. RESULTS: Histopathological and immunohistochemical study of the tumor showed it to be an adenocarcinoma of the RPE. CONCLUSIONS: Adenocarcinoma of the RPE arising from CHRPE is extremely rare. Such a tumor can resemble a choroidal melanoma. In spite of the rarity of this association, periodic monitoring of CHRPE for development of a nodular tumor of the RPE is probably warranted.

Adenocarcinoma↗

Population-based incidence of uveal melanoma in various races and ethnic groups.

PURPOSE: To investigate racial/ethnic differences in the development of uveal malignant melanoma in a large population-based study. DESIGN: Observational cross-sectional study. METHODS: With the 1992 to 2000 data that was provided by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program, we calculated age-adjusted incidence rates of uveal melanoma in various racial/ethnic groups (black, Asian and Pacific Islander, Hispanic, and non-Hispanic white). In addition, we calculated the standard incidence ratio (risk ratio) and 95% confidence interval to describe the differences within these racial/ethnic groups. RESULTS: From 1992 to 2000, there were a total of 1352 uveal melanomas that were diagnosed in 11 Surveillance, Epidemiology, and End Results registries with known racial/ethnic groups. The annual age-adjusted incidence (per million population) of uveal melanoma was 0.31 (black), 0.38 (Asian), 1.67 (Hispanic), and 6.02 (non-Hispanic white). The difference in the incidence of uveal melanoma between each racial/ethnic group was highly statistically significant, with the exception of the black versus the Asian population in which there was no statistically significant difference. CONCLUSION: The relative risk of uveal melanoma was 1.2 for Asian and Pacific Islander patients, 5.4 for Hispanic patients, and 19.2 for non-Hispanic white patients as compared with the black patients. If the non-Hispanic white population and the Hispanic population were combined, then the overall white:black ratio was 18:1.

Cross-Sectional Studies↗

A case of primary adenocarcinoma of the lacrimal sac.

PURPOSE: To present a rare case of adenocarcinoma arising from the lacrimal sac. DESIGN: Interventional case report. METHODS: Report of a new case of primary lacrimal sac adenocarcinoma. RESULTS: The clinical presentation, workup, surgical treatment and pathology of a case of adenocarcinoma of the lacrimal sac are described. CONCLUSION: Although very rare, these tumors should be in the differential diagnosis of any lacrimal sac mass, especially those presenting above the medial canthal tendon. Other common features include expressible blood from the punctum, lack of pain, and a history of chronic epiphora or intermittent dacryocystitis. Local destruction and metastatic spread can be prevented by a high index of suspicion and early intervention.

Adenocarcinoma↗

Advanced periocular, facial, and oral amyloidosis.

A 57-year-old white man presented with extensive bilateral, symmetric, confluent papules involving the upper and lower eyelids, causing visual impairment and cosmetic deformity. Surgical debulking of the papules was initially performed, but the lesion rapidly recurred and enlarged. Histopathologic examination revealed cutaneous amyloidosis. Six months later, extensive excision of the upper eyelid lesions was required to restore normal visual function.

Amyloidosis↗

High-frequency ultrasound of anterior segment retinoblastoma.

PURPOSE: To evaluate anterior segment retinoblastoma with high-frequency ultrasound. DESIGN: Interventional case report. METHODS: An 11-year-old boy with a total retinal detachment and multiple white anterior chamber nodules was examined with high-frequency ultrasound before enucleation of the globe. RESULTS: Multiple solid and cystic nodular tumors were found in the anterior chamber angle. With high-frequency ultrasound, tumor was discovered posterior to the iris, over the ciliary processes, and on the lens capsule. No calcifications were noted. Other findings included angle closure related to iris neovascularization and uveal thickening. CONCLUSION: High-frequency ultrasound can be used to evaluate retinoblastoma extension into the anterior segment. These images may be used for comparison in future cases of retinoblastoma with anterior chamber invasion.

Anterior Eye Segment↗

Visual recovery after radiation therapy for bilateral subfoveal acute myelogenous leukemia (AML).

PURPOSE: Present a case of bilateral foveal acute myelogenous leukemic tumors that responded to radiation therapy. DESIGN: Case report. METHODS: A patient was diagnosed with bilateral subfoveal infiltration of known systemic acute myelogenous leukemia. He received a standard induction chemotherapy, followed by consolidation therapy for his systemic leukemia. However, despite a complete marrow response, the intraocular tumors did not regress. Therefore, he was given low dose (1950-cGy) ocular external beam radiation therapy. RESULTS: One course of systemic cytarabine chemotherapy failed to control the subfoveal tumors, leaving the patient at risk for permanent vision loss. In contrast, external beam radiation therapy improved his vision from 20/60 in his right eye to 20/20 and from 20/70 in his left eye to 20/25. CONCLUSION: Although systemic chemotherapy can be used to treat intraocular metastasis, external beam radiation may provide more prompt resolution of vision-threatening tumors.

Adult↗

Enucleation versus preservation of blind eyes following plaque radiotherapy for choroidal melanoma.

BACKGROUND: Currently available information about patients with posterior uveal melanoma treated by plaque radiotherapy is insufficient to determine what to do about eyes that become blind as a consequence of the tumour and its treatment. Should they be enucleated, or is ocular preservation just as good in terms of survival? METHODS: We performed a retrospective survival analysis of secondary enucleation versus ocular preservation in patients with a posterior uveal melanoma treated by plaque radiotherapy whose irradiated eye became completely blind following that treatment. Of the 79 patients who fulfilled defined inclusion criteria, 25 underwent secondary enucleation of the blind eye, and 54 retained their irradiated blind eye. RESULTS: Most of the baseline demographic and tumour-related variables evaluated were similarly distributed between the subgroups. The 5-year, 10-year and 15-year all-cause death rates in the secondary enucleation subgroup were 24.7%, 51.5% and 52.0% respectively, and those in the ocular preservation subgroup were 7.4%, 32.9% and 48.1% respectively. In spite of the apparent slight difference between the curves, the difference was not statistically significant (p = 0.41, Mantel-Haenszel test). INTERPRETATION: Although a retrospective study of this type has several limitations, our results suggest that secondary enucleation is not likely to substantially improve survival of patients whose irradiated eye becomes totally blind following plaque radiotherapy for choroidal or ciliochoroidal melanoma.

Blindness↗

Plaque radiotherapy for choroidal and ciliochoroidal melanomas with limited nodular extrascleral extension.

BACKGROUND: Currently available clinical information regarding management of posterior uveal melanomas complicated by nodular extrascleral extension is inadequate to determine the role, if any, for plaque radiotherapy in such patients. METHODS: The authors performed a retrospective descriptive study of eight patients with a choroidal or ciliochoroidal melanoma complicated by nodular extrascleral extension who were treated by surgical excision of the extrascleral nodule followed immediately by plaque radiotherapy of the intraocular tumour. The calculated volume of the extrascleral nodule was greater than 1 mm3 but less than 1000 mm3 in all cases, and the intraocular tumour was deemed treatable by plaque radiotherapy in all patients. RESULTS: Four of the eight patients died during available follow-up, three from metastatic melanoma and one from a second cancer. The median length of follow-up for the four surviving patients was 10.1 years. The actuarial 5-year and 10-year all-cause death rates were 37.5% and 53.1% respectively. One of the eight patients experienced local intraocular tumour relapse following plaque therapy and underwent secondary enucleation. None of the patients experienced orbital tumour recurrence or underwent secondary orbital exenteration. INTERPRETATION: Our results coupled with previously published results from another centre suggest that plaque radiotherapy may be an effective local treatment for selected patients with choroidal or ciliochoroidal melanoma complicated by nodular extrascleral extension. The fact that none of the patients in this series or in the previously reported series experienced orbital recurrence following plaque radiotherapy or required secondary orbital exenteration suggests that plaque therapy may be better than enucleation alone in terms of these end points. These results should not be extrapolated, of course, to patients with massive extrascleral tumour extension or a choroidal or ciliochoroidal melanoma too large for plaque radiotherapy.

Aged↗

Malignant mesenchymoma of the orbit: case report and review of the literature.

OBJECTIVE: Malignant mesenchymoma are rare tumors of the orbit. From 1961 using English-language literature, we present the sixth such case and the first case with three malignant components. DESIGN: Interventional case report. METHODS: The clinical presentation, workup, surgical treatment, and pathology of a case of malignant mesenchymoma of the orbit are presented. RESULTS: Although very rare, these tumors should be in the differential diagnosis of any tumor of the orbit. The prognosis is unknown because of the lack of follow-up of reported patients. CONCLUSIONS: This malignant orbital mesenchymoma, an entity not accepted by all pathologists, was more complex than cases previously reported in the English literature in demonstrating rhabdomyosarcomatous, chondrosarcomatous, and osteogenic differentiation.

Aged↗

Solitary fibrous tumor of the orbit: is it rare? Report of a case series and review of the literature.

PURPOSE: The real incidence of solitary fibrous tumor (SFT) of the orbit is unknown, but it seems that since it was first described in 1994, orbital SFT has been increasingly recognized. We believe that the orbital SFT is a relatively common tumor and that it should be considered in the differential diagnosis of any orbital tumor. DESIGN: Interventional case series. PARTICIPANTS: Four new cases of orbital SFT. METHODS: Four patients affected by solitary fibrous tumor of the orbit are described. One patient experienced a recurrent SFT shortly after initial surgical excision performed elsewhere. Thirty-eight cases have been reported in the literature in 7 years. RESULTS: The number of orbital SFTs reported has been increasing, reaching an average of more than five tumors reported per year. Since the first orbital SFT was described in 1994, 37 cases have been reported in the literature. We add four new cases in our series, including a recurrent tumor. A total of 42 cases have now been described, eight with recurrences. Malignant transformation occurred in one case. CONCLUSIONS: We believe that before 1994, the diagnosis orbital SFT was confused with other benign orbital tumors, such as fibrous histiocytoma and hemangiopericytoma because of a lack of use of immunohistochemical techniques. This entity should now be considered relatively common and should be included in the differential diagnosis of orbital tumors in any age group. Local recurrences of SFT are possible and usually follow an incomplete initial excision. Recurrent tumors in the orbit have shown the tendency to infiltrate the surrounding tissues and the bone, rendering complete secondary excision more difficult. Recurrent orbital SFT also has the potential for malignant transformation. The treatment of choice of orbital SFT is complete surgical excision and careful follow-up. Considering the more aggressive course followed by recurrent tumor, correct diagnosis and management is essential.

Adult↗

Thinning of the anterior capsule associated with congenital aniridia.

PURPOSE: To report the unusual finding of intraoperative fragility of the anterior capsule in some patients with congenital aniridia and determine the histopathologic etiology of this finding. SETTING: Cincinnati Eye Institute, Cincinnati, Ohio, USA. METHODS: Anterior lens capsule specimens were obtained from aniridic and nonaniridic patients during cataract surgery. The intraoperative behavior of each capsule was noted, after which the specimens were submitted for histopathologic evaluation. RESULTS: All anterior capsule specimens from the nonaniridic patients were of normal thickness. Some, but not all, anterior capsule specimens from the aniridic patients were remarkably thin. Thin capsules were associated with extreme intraoperative fragility. CONCLUSIONS: Greater awareness of anterior capsule fragility in some aniridic patients may reduce the risk of capsule complications and lead to safer surgical outcomes.

Adult↗